Pupillometry: Arousal State or State of Mind?

Norepinephrine and acetylcholine regulate brain activity during changes in arousal attention that are also reflected fluctuations of the pupil. New research suggests goal-directed behavior, serotonin is associated with pupil dilation. Light enters eye through — an opening center iris, central part defines our color contains musculature to control size. When we step outdoors into bright sunshine, pupils reduce size (constriction) limit amount light eye. Conversely, when brightness decreases, opens up (dilation) admit more light. In addition this prosaic function as a gatekeeper photons, fluctuates emotional state such fear or empathy, behavioral states level (whether one focused on task not) (or alertness, ranging from hypervigilant drowsy), sudden environment, for example something happens violates expectation1Joshi S. Gold J.I. Pupil window neural substrates cognition.Trends Cogn. Sci. 2020; 24: 466-480Abstract Full Text PDF PubMed Scopus (41) Google Scholar. Brain factors regulated by norepinephrine (NE), (ACh) (5HT) acting neuromodulators chemicals not driving but rather modulating ongoing neurons. For these reasons, covary environmental and/or often taken indicators neuromodulator levels brain1Joshi Scholar,2Nieuwenhuis De Geus E.J. Aston-Jones G. The anatomical functional relationship between P3 autonomic components orienting response.Psychophysiology. 2011; 48: 162-175Crossref (264) But how reliable indicator can it distinguish effects they fluctuate simultaneously? Results increasing number studies starting reveal what (and cannot) learn about pupillometry measurement reactivity. example, recent showed covariations NE ACh neuromodulatory systems3Joshi Li Y. Kalwani R.M. Relationships diameter neuronal locus coeruleus, colliculi, cingulate cortex.Neuron. 2016; 89: 221-234Abstract (502) Scholar, 4Nelson A. Mooney R. basal forebrain motor cortex provide convergent yet distinct movement-related inputs auditory 90: 635-648Abstract (72) 5Reimer J. McGinley M.J. Liu Rodenkirch C. Wang Q. McCormick D.A. Tolias A.S. track rapid adrenergic cholinergic cortex.Nat. Commun. 7: 13289Crossref (276) Such findings have started empirical basis interpreting measurements terms activity. However, neuromodulation complex, behaviors remains under-explored. A new study Cazettes et al.6Cazettes F. Reato D. Morais J.P. Renart Mainen Z.F. Phasic activation dorsal raphe serotonergic neurons increases size.Curr. Biol. 2021; 31: 192-197Abstract (6) Scholar reported issue Current Biology fills important gap knowledge. These authors measured behavior system head-fixed mice performing foraging task. They found transient dilations were evoked optogenetic stimulation 5-HT nucleus depended task-related uncertainty. trained forage water among two sources. included group, SERT-Cre mice, 5HT nucleus, second group wild-type littermates. Both groups implanted optic-fiber cannulas delivering stimulating pulses nucleus. Corroborating previous studies, under range conditions: spontaneously remained still; locomotion; licking. Next, temporally aligned onset lick bouts, resulted their Using model explore reliance neurons, reliably baseline size, licking locomotion. During there was dependence predictor only larger effect longer duration. further did depend locomotion traditionally used index global state. So what, if state, stimulation-induced dilation associated? To further, reward uncertainty stimulation. required choose sources water, which could deliver at any moment. mouse licked chosen source, probabilistic both delivery depletion. By changing probability depletion, able manipulate environment. depletion high, site be gauged relatively high certainty after few exploratory, unrewarded licks. reducing probabilities leads greater uncertainty: low combined perplexed (but, hopefully sake experimenters, persistent) mouse. Previous work has shown reflect environment7Preuschoff K. 't Hart B.M. Einhäuser W. signals surprise: evidence noradrenaline's role decision making.Front. Neurosci. 5: 115Crossref (242) affects sensitivity reward8Bari Theobald D.E. Caprioli Mar A.C. Aidoo-Micah Dalley J.W. Robbins T.W. Serotonin modulates negative feedback reversal learning rats.Neuropsychopharmacology. 2010; 35: 1290-1301Crossref (181) might signal prediction error (the difference actual outcome predicted outcome)9Matias Lottem E. Dugué G.P. Activity patterns underlying cognitive flexibility.eLife. 2017; 6e20552Crossref (80) caused condition than condition. conclude transients acted prediction-error-like signal. Naturally occurring rare condition, so artificial, act same way surprise dilations2Nieuwenhuis Scholar,3Joshi likely quite frequent adding via makes them even less surprising events, consistent smaller no stimulation, licking, model, modulator Although changed uncertainty, dependent Neuromodulatory systems other nucleus-5HT previously been Notably, coeruleus-norepinephrine (LC-NE) forebrain-acetylcholine (BF-ACh) size1Joshi implicated key translators while reflecting attentive state1Joshi Scholar,10Dayan P. Twenty-five lessons computational neuromodulation.Neuron. 2012; 76: 240-256Abstract (101) Much needed understand systems, all brain-wide projections, similar different circuits, This includes simultaneous multiple experimental designs probe sensory, factors. know LC-NE system, passive evokes dilations3Joshi One question arising is: do vary not? Another affect circuits regions project. timing (transient versus gradual) dynamically sculpt coordinated populations influence thus affecting information encoding capacity networks active behaviors11Joshi Context-dependent relationships coeruleus firing anterior cortex.bioRxiv. https://doi.org/10.1101/2020.09.26.314831Crossref (0) Scholar,12Tervo D.G.R. Proskurin M. Manakov Kabra Vollmer Branson Karpova A.Y. Behavioral variability stochastic choice its gating cortex.Cell. 2014; 159: 21-32Abstract (115) Are BF-ACh systems? Changes (along locomotion) widely term generally characterize whether subject drowsy (low state) alert (increased state). change actively engaged behaviors, including What indicate? There that, level, factors13Jepma Nieuwenhuis predicts exploration-exploitation trade-off: adaptive gain theory.J. 23: 1587-1596Crossref (236) 14Nassar M.R. Rumsey K.M. Wilson R.C. Parikh Heasly B. Rational regulation dynamics pupil-linked systems.Nat. 15: 1040-1046Crossref (308) 15Filipowicz A.L. Glaze C.M. Kable encodes idiosyncratic, complexity belief updating.eLife. 9e57872Crossref (9) factors, expectation violation error, computations encoded prefrontal cortical regions12Tervo Scholar,16Matsumoto Matsumoto Abe H. Tanaka Medial cell signaling errors action values.Nat. 2007; 10: 647-656Crossref (315) Scholar,17Padoa-Schioppa Conen K.E. Orbitofrontal cortex: circuit economic decisions.Neuron. 96: 736-754Abstract (99) Subsets descending nuclei LC nucleus18Geddes S.D. Assadzada Lemelin Sokolovski Bergeron Haj-Dahmane Béïque J.C. Target-specific modulation cannabinoids.Proc. Natl. Acad. USA. 113: 5429-5434Crossref (45) 19Arnsten A.F. Goldman-Rakic P.S. Selective projections region rhesus monkey.Brain Res. 1984; 306: 9-18Crossref (225) 20Stanton G.B. Goldberg M.E. Bruce C.J. Frontal field efferents macaque monkey: II. Topography terminal fields midbrain pons.J. Comp. Neurol. 1988; 271: 493-506Crossref (300) (Figure 1)1Joshi Thus, some conditions, indicate simply ‘state’. Whether decode seen. Towards end, link specific indexed Activation Dorsal Raphe Serotonergic Neurons Increases SizeCazettes al.Current BiologyNovember 12, 2020In BriefThe (5-HT) investigated detail. al. show phasic causes variables appear linked statistics. Full-Text Open Access