Biology subjects

Wen, T.

Publications and source records attributed to Wen, T..

3 recordsLinked to original sources

bioRxiv2018

Connectivity Patterns in Cognitive Control Networks Predict Naturalistic Multitasking Ability

Multitasking is a fundamental aspect of everyday life activities. To achieve a complex, multi-component goal, the tasks must be subdivided into sub-tasks and component steps, a critical function of prefrontal networks. The prefrontal cortex is considered to be organized in a cascade of executive processes from the sensorimotor to anterior prefrontal cortex, which includes execution of specific goal-directed action, to encoding and maintaining task rules, and finally monitoring distal goals. In the current study, we used a virtual multitasking paradigm to tap into real-world performance and relate it to each individuals resting-state functional connectivity in fMRI. While did not find any correlation between global connectivity of any of the major networks with multitasking ability, global connectivity of the lateral prefrontal cortex (LPFC) was predictive of EVET score. Further analysis showed that multivariate connectivity patterns within the sensorimotor network (SMN), and between-network connectivity of the frontopartietal network (FPN) and dorsal attention network (DAN), predicted individual multitasking ability and could be generalized to novel individuals. Together, these results support previous research that prefrontal networks underlie multitasking abilities and show that connectivity patterns in the cascade of prefrontal networks may explain individual differences in performance.

neuroscience↗

bioRxiv2018

Response of the multiple-demand network during simple stimulus discriminations

The multiple-demand (MD) network is sensitive to many aspects of task difficulty, including such factors as rule complexity, memory load, attentional switching and inhibition. Many accounts link MD activity to top-down task control, raising the question of response when performance is limited by the quality of sensory input, and indeed, some prior results suggest little effect of sensory manipulations. Here we examined judgments of motion direction, manipulating difficulty by either motion coherence or salience of irrelevant dots. We manipulated each difficulty type across six levels, from very easy to very hard, and additionally manipulated whether difficulty level was blocked, and thus known in advance, or randomized. Despite the very large manipulations employed, difficulty had little effect on MD activity, especially for the coherence manipulation. Contrasting with these small or absent effects, we observed the usual increase of MD activity with increased rule complexity. We suggest that, for simple sensory discriminations, it may be impossible to compensate for reduced stimulus information by increased top-down control.

neuroscience↗

bioRxiv2018

The Specificity of IQGAP1 Toward the PI3K-Akt Pathway is Dependent on the IQ3 motif

Epidermal growth factor receptor (EGFR) and its downstream phosphatidylinositol 3-kinase (PI3K) pathway are commonly deregulated in many cancers including head and neck cancer (HNC). Recently, we have shown that the IQ motif-containing GTPase-activating protein 1 (IQGAP1) provides a molecular platform to scaffold all the components from the PI3K-Akt pathway and results in the sequential generation of phosphatidylinositol-3,4,5-triphosphate (PI3,4,5P3). This makes the IQGAP1-PI3K scaffold a promising therapeutic target. In addition to the PI3K-Akt pathway, IQGAP1 also scaffolds the Ras-ERK pathway. To identify an IQGAP1 mutant that specifically loses IQGAP1-PI3K signaling but not other functions, we have focused on the IQ3 motif since this region binds with both the PIPK1 and PI3K enzymes and a short peptide derived from this sequence blocks binding and PI3K signaling. An IQ3 deletion mutant ({Delta}IQ3) in IQGAP1 was functionally compared with wild-type (WT) IQGAP1. We found that the IQ3 domain specifically mediates the PI3K-Akt pathway but does not regulate the Ras-ERK pathway. The IQ3 deletion mutant lost interactions with PI3K-Akt components but retained its binding of ERK pathway components and cell surface receptors, EGFR and integrins. In addition, the IQ3 deletion mutant lost regulation of cell migration. Consistently, the IQ3 motif derived peptide blocked Akt activation and led to the blockage of invasion mediated by EGFR organized into an integrin complex by syndecan-4. Taken together, this work has defined the IQGAP1 IQ3 motif as a specific target sequence for the scaffolding of the PI3K-AKT pathway.

cell biology↗