PROJECT SUMMARY / ABSTRACT Different sensory modalities elicit distinct neural signatures in the brain, however, a fundamental subset of circuits for perception is shared across modalities. Subcortical arousal systems are known to influence long- lasting states such as sleep/wake and levels of vigilance, but their role in dynamic short-term modulation of arousal shared across perceptual modalities has been little studied. Subcortical systems are increasingly recognized as playing an important role in cognition. Recent work suggests that multiple parallel arousal systems in the thalamus, upper brainstem and basal forebrain contribute to phasic modulation of perception through a transient increase in activity following sensory stimuli. Therefore, our central hypothesis is that a transient pulse of activity in the intralaminar thalamus, upper brainstem and basal forebrain occurs after sensory stimuli across diverse modalities, augmenting perceptual awareness. If confirmed, this may identify both fundamental circuits for normal perception and potential therapeutic targets for disorders where perception is impaired. We will investigate shared subcortical arousal circuits in perception using techniques with complementary strengths based on promising initial studies. We found that large fMRI data sets showed shared transient activation in thalamus, midbrain and basal forebrain with visual, tactile and gustatory tasks. To investigate this further, our first aim will contrast perceived vs not perceived visual, auditory and tactile stimuli to study shared fMRI signals in subcortical arousal areas with both whole brain and high-resolution subcortical methods. In our second aim, we will leverage recent findings that pupil, blink and microsaccade measurements combined with machine learning can isolate the components of subcortical perception-related fMRI signals which are independent of task report. These methods will be used to identify shared fMRI signals in subcortical arousal systems with visual, auditory and tactile perception independent of report. Finally, direct access to the human intralaminar thalamus through devices implanted in epilepsy patients, provides a unique opportunity for both thalamic recording and stimulation. In our third aim, we will use this approach to record and stimulate the intralaminar thalamus to determine the role of this key subcortical arousal area in perception. Understanding the role of transient increases in subcortical arousal shared across perceptual modalities will both shed light on fundamental mechanisms of perception, and provide new treatment avenues for perceptual disorders.