I think that the most exciting insights into brain (dys)function come from integrating across different scales of analysis and understanding: from measurements
and manipulations of neural circuits and individual neurons in animals to measurements of brain-wide networks in humans. It is from this perspective at the
interface of computational, cognitive and systems neuroscience that I want to build an independent research program. I'm specially interested in how
neuromodulatory signals shape perception and decision-making, and how disturbances in neuromodulatory circuits are implicated in various clinical disorders,
ranging from disorders of consciousness to ADHD.
As a Postdoctoral Associate in the lab of Dr. Matthew McGinley my goal was to
uncover how neuromodulatory-sensory interactions implement motivated shifts in attentional (listening) effort. I have also helped to establish
the first vagus nerve stimulation approach in head-fixed mice.
Graded recruitment of pupil-linked neuromodulation by parametric stimulation of the vagus nerve. 2019. bioRxiv.
Vagus nerve stimulation (VNS) is thought to alter the state of the brain by recruiting global neuromodulators. VNS is used in treatment-resistant epilepsy,
and is increasingly being explored for other brain 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 biosensor for assaying stimulation efficacy in real time. We here develop an approach to VNS in head-fixed mice on a treadmill, and use it to show
that pupil dilation is a biosensor for VNS-evoked cortical neuromodulation. In a ‘goldilocks’ 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 auditory cortex. Thus, pupil dilation
is a sensitive readout of the moment-by-moment titratable effects of VNS on brain state.
My PhD track with Prof. Dr. Tobias Donner
was centered around the question how global
neuromodulatory signals shape cognitive processes unfolding in cortex, such as decisions. I tested specific theoretical predictions with an integrative approach
that combined behavioral analysis, pupilollometry, human electrophysiology, human neuroimaging, pharmacological intervention, and computational modeling, all
focusing on a common behavioral task.
Pupil-linked phasic arousal predicts a reduction of choice bias across species and decision domains. 2020. eLife, 9, e54014.
Decisions are often made by accumulating ambiguous evidence over time. The brain’s arousal systems are activated during such decisions. In previous work in humans,
we found that evoked responses of arousal systems during decisions are reported by rapid dilations of the pupil and track a suppression of biases in the accumulation
of decision-relevant evidence (de Gee et al., 2017). Here, we show that this arousal-related suppression in decision bias acts on both conservative and liberal biases,
and generalizes from humans to mice, and from perceptual to memory-based decisions. In challenging sound-detection tasks, the impact of spontaneous or experimentally
induced choice biases was reduced under high phasic arousal. Similar bias suppression occurred when evidence was drawn from memory. All of these behavioral effects
were explained by reduced evidence accumulation biases. Our results point to a general principle of interplay between phasic arousal and decision-making.
Dynamic modulation of decision biases by brainstem arousal systems. 2017. eLife, 6, e23232.
Decision-makers often arrive at different choices when faced with repeated presentations of the same evidence. Variability of behavior is commonly attributed to
noise in the brain’s decision-making machinery. We hypothesized that phasic responses of brainstem arousal systems are a significant source of this variability.
We tracked pupil responses (a proxy of phasic arousal) during sensory-motor decisions in humans, across different sensory modalities and task protocols. Large pupil
responses generally predicted a reduction in decision bias. Using fMRI, we showed that the pupil-linked bias reduction was (i) accompanied by a modulation of choice-
encoding pattern signals in parietal and prefrontal cortex and (ii) predicted by phasic, pupil-linked responses of a number of neuromodulatory brainstem centers
involved in the control of cortical arousal state, including the noradrenergic locus coeruleus. We conclude that phasic arousal suppresses decision bias on a
trial-by-trial basis, thus accounting for a significant component of the variability of choice behavior.
Decision-related pupil dilation reflects upcoming choice and individual bias. 2014. PNAS, 111(5), E618-E625.
A number of studies have shown that pupil size increases transiently during effortful decisions. These decision-related changes in pupil size are mediated by
central neuromodulatory systems, which also influence the internal state of brain regions engaged in decision making. It has been proposed that pupil-linked
neuromodulatory systems are activated by the termination of decision processes, and, consequently, that these systems primarily affect the postdecisional brain
state. Here, we present pupil results that run contrary to this proposal, suggesting an important intradecisional role. We measured pupil size while subjects
formed protracted decisions about the presence or absence (“yes” vs. “no”) of a visual contrast signal embedded in dynamic noise. Linear systems analysis
revealed that the pupil was significantly driven by a sustained input throughout the course of the decision formation. This sustained component was larger
than the transient component during the final choice (indicated by button press). The overall amplitude of pupil dilation during decision formation was bigger
before yes than no choices, irrespective of the physical presence of the target signal. Remarkably, the magnitude of this pupil choice effect (yes > no) reflected
the individual criterion: it was strongest in conservative subjects choosing yes against their bias. We conclude that the central neuromodulatory systems
controlling pupil size are continuously engaged during decision formation in a way that reveals how the upcoming choice relates to the decision maker’s
attitude. Changes in brain state seem to interact with biased decision making in the face of uncertainty.