Browsing by Author "de Gee, Jan Willem"

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    Graded recruitment of pupil-linked neuromodulation by parametric stimulation of the vagus nerve
    (Springer Nature, 2021) Mridha, Zakir; de Gee, Jan Willem; Shi, Yanchen; Alkashgari, Rayan; Williams, Justin; Suminski, Aaron; Ward, Matthew P.; Zhang, Wenhao; McGinley, Matthew James
    Vagus nerve stimulation (VNS) is thought to affect neural activity by recruiting brain-wide release of neuromodulators. VNS is used in treatment-resistant epilepsy, and is increasingly being explored for other disorders, such as depression, and as a cognitive enhancer. However, the promise of VNS is only partially fulfilled due to a lack of mechanistic understanding of the transfer function between stimulation parameters and neuromodulatory response, together with a lack of biosensors for assaying stimulation efficacy in real time. We here develop an approach to VNS in head-fixed mice on a treadmill and show that pupil dilation is a reliable and convenient biosensor for VNS-evoked cortical neuromodulation. In an ‘optimal’ zone of stimulation parameters, current leakage and off-target effects are minimized and the extent of pupil dilation tracks VNS-evoked basal-forebrain cholinergic axon activity in neocortex. Thus, pupil dilation is a sensitive readout of the moment-by-moment, titratable effects of VNS on brain state.
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    Strategic stabilization of arousal boosts sustained attention
    (Elsevier, 2024) de Gee, Jan Willem; Mridha, Zakir; Hudson, Marisa; Shi, Yanchen; Ramsaywak, Hannah; Smith, Spencer; Karediya, Nishad; Thompson, Matthew; Jaspe, Kit; Jiang, Hong; Zhang, Wenhao; McGinley, Matthew J.
    Arousal and motivation interact to profoundly influence behavior. For example, experience tells us that we have some capacity to control our arousal when appropriately motivated, such as staying awake while driving a motor vehicle. However, little is known about how arousal and motivation jointly influence decision computations, including if and how animals, such as rodents, adapt their arousal state to their needs. Here, we developed and show results from an auditory, feature-based, sustained-attention task with intermittently shifting task utility. We use pupil size to estimate arousal across a wide range of states and apply tailored signal-detection theoretic, hazard function, and accumulation-to-bound modeling approaches in a large cohort of mice. We find that pupil-linked arousal and task utility both have major impacts on multiple aspects of task performance. Although substantial arousal fluctuations persist across utility conditions, mice partially stabilize their arousal near an intermediate and optimal level when task utility is high. Behavioral analyses show that multiple elements of behavior improve during high task utility and that arousal influences some, but not all, of them. Specifically, arousal influences the likelihood and timescale of sensory evidence accumulation but not the quantity of evidence accumulated per time step while attending. In sum, the results establish specific decision-computational signatures of arousal, motivation, and their interaction in attention. So doing, we provide an experimental and analysis framework for studying arousal self-regulation in neurotypical brains and in diseases such as attention-deficit/hyperactivity disorder.