Friday, May 9, 2025
5/9/2025
Pupillary working memory for adaptive perception - PROJECT SUMMARY Goal-directed perception and cognition rest on the ability to keep target information activated in mind, through periods when it is unavailable in the sensory environment. This working memory can serve to track occluded objects, wield goal templates for visual search, and retain a coherent representation of the visual world as the eyes move around. Working memory is considered an endogenous internal maintenance function, but successful behavior must also adjust goals in reaction to external conditions. Likewise, failure to integrate relevant sensory content into working memory, or to shield internal goal content from interfering input, are both uniquely characteristic of several neurological and psychiatric disorders. Yet the mechanisms that adaptively promote or prevent interactions between perception and working memory have been perplexing to isolate, and it is broadly contested how and where working memory information is stored. In addition to known fronto- parietal substrates, recent findings show that working memory engages distributed activations throughout subcortical and sensorimotor regions, and may further recruit the peripheral nervous system and sensorimotor apparatus. For instance, during a blank working memory delay, gaze and involuntary eye movements veer toward the location where a working memory item was encoded, and changes in pupil size track its remembered brightness. Such oculomotor and peripheral measurements have become widely adopted as indices of neuro-cognitive processing, but it is unknown what underlying activity they reflect and if they serve any functional role. This proposal tests the possibility that peripheral modulation, and pupil control in particular, may be a sensitive instrument to align internal goals and perceptual processing. Although the eyes are considered windows to underlying states, they do more than pass data through—they also modulate and filter what we extract from the environment. Rather than recapitulate neural activity, pupillary responses may subtly mold cortical working memory traces, hold the eyes in a goal-ready configuration, or bias visual perception in line with working memory features. The proposed studies will systematically test these possibilities in humans. The project will combine physiological measurements (fMRI and eye-tracking) with transcranial stimulation (TMS), to test the causal relationships between peripheral modulation, neural working memory signatures, and behavior. Specific Aims will test whether pupillary working memory signals convey behavioral relevance and decisional quality (Aim 1), configure to the predictive task context (Aim 2), or shape and interact with ongoing perception (Aim 3). This work will test the boundaries of cognitive influence on pupillary function, revealing new working memory mechanisms and unboxing potential for pupil states to be volitionally controlled. Every Aim will perturb activity at critical visuo-oculomotor loci, to dissect the underlying circuitry and define the information contained within cognitive pupillary inflections. This clarity will be essential in order to harness these integrative signals toward better methods for gauging and treating sources of visual and cognitive dysfunction.
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