Waking State: Rapid Variations Modulate Neural and Behavioral Responses

In the paper

“Falling asleep, or moving from slow wave sleep into rapid eye movement sleep, results in profound changes in the operation of the brain (Figure 1), including changes in spontaneous activity, the ability to execute motor commands, responses to sensory stimuli and the fidelity of internal representations of the world”

What the sources say

• Not checked yetcites Destexhe et al., 1999 source
• Not checked yetcites Steriade et al., 2001 source

In the paper

“Recently, the marked impact of apparent spontaneous variations in the human waking state on both cortical responses and perceptual abilities has begun to be more widely appreciated”

What the sources say

• Not checked yetcites Boly et al., 2007 source
• Not checked yetcites Fox and Raichle, 2007 source
• Not checked yetcites He, 2013

In the paper

“By comparison, the variations in neural activity within the waking state due to changes in factors such as arousal, attention, and awareness are ostensibly less dramatic and therefore the mechanisms of waking state variations have remained more elusive”

What the sources say

• Not checked yetcites Harris and Thiele, 2011
• Not checked yetcites Zagha and McCormick, 2014

In the paper

“During periods of quiet wakefulness (lacking overt movement), large low-frequency (< 10 Hz) fluctuations in the synaptic activity of somatosensory, visual, and auditory cortical neurons are frequently observed, and these oscillations are strongly suppressed by the initiation of whisking or locomotion”

What the sources say

• Not checked yetcites Bennett et al., 2013 source
• Not checked yetcites Crochet and Petersen, 2006
• Not checked yetcites McGinley et al., 2015 source

In the paper

“This slow oscillation is cortically generated but influences activity throughout the brain”

What the sources say

• Not checked yetcites Ros et al., 2009 source
• Not checked yetcites Steriade et al., 1993 source
• Not checked yetcites Steriade et al., 2001 source

In the paper

“All together, these biomarkers for waking states predict changes in the capability of animals to represent and respond to stimuli, and account for a significant fraction of the variability in spontaneous and stimulus-driven activity and behavior.”

In the paper

“Classically, slow wave sleep is characterized by a high density of cortical field potential power at 0.5–4 Hz, reduced muscle tone, and rolling eye movements, while waking is associated with a relative suppression of low frequency activity (usually termed “activation” or “desynchronization”), increased muscle tone, and behaviorally relevant eye movements”

What the sources say

• Not checked yetcites Kryger et al., 2010

In the paper

“Human and animal studies have shown that changes in pupil diameter (after controlling for changes associated with luminance and depth accommodation) are correlated with arousal, attention, emotion, cognitive perception, “brain gain”, as well as heart rate and galvanic skin reflex, indicating a tight coupling between the state of the central and peripheral nervous systems”

What the sources say

• Not checked yetcites Alnaes et al., 2014
• Not checked yetcites Bradley et al., 2008 source
• Not checked yetcites Kahneman and Beatty, 1966

In the paper

“This work has revealed that spontaneous and sensory-evoked activity varies continuously and rapidly during wakefulness.”

What the sources say

• Not checked yetcites McGinley et al., 2015 source
• Not checked yetcites Reimer et al., 2014 source
• Not checked yetcites Vinck et al., 2015 source

In the paper

“Additionally, the relationship between cortical membrane potential and pupil diameter is influenced by the presence of slow oscillations at low arousal states and strong barrages of synaptic activity and/or tonic depolarization at high arousal states”

What the sources say

• Not checked yetcites McGinley et al., 2015 source

In the paper

“Even in the absence of movement, increases in pupil diameter (dilation) were found to be associated with increases in cortical activation and suppression of low frequency rhythms.”

What the sources say

• Not checked yetcites McGinley et al., 2015 source
• Not checked yetcites Reimer et al., 2014 source
• Not checked yetcites Vinck et al., 2015 source

In the paper

“At these intermediate arousal levels, the average membrane potential of infragranular cortical neurons is at its most hyperpolarized, and least variable, level”

What the sources say

• Not checked yetcites McGinley et al., 2015 source

In the paper

“Increases from intermediate to high arousal associated with brief (microdilations) or long-lasting increases in pupil diameter (often associated with locomotion), result in a depolarization of the membrane potential and increases in high-frequency membrane potential fluctuations from synaptic barrages”

What the sources say

• Not checked yetcites McGinley et al., 2015 source

In the paper

“Even in seemingly stable emotional states, pupil diameter can fluctuate with effort on a task (e.g. difficulty of performing a mathematical calculation) (Kahneman and Beatty, 1966), the timing of mental decisions (Einhauser et al., 2010), or changes in perception (e.g. with binocular rivalry) (Einhauser et al., 2008).”

What the sources say

• Not checked yetcites Kahneman and Beatty, 1966
• Not checked yetcites Einhauser et al., 2010
• Not checked yetcites Einhauser et al., 2008 source

In the paper

“Increases in arousal from low to intermediate levels result in a suppression of these low (1–10 Hz) frequency activities, a decrease in membrane potential fluctuations, and thus a decrease in spontaneous activity”

What the sources say

• Not checked yetcites McGinley et al., 2015 source

In the paper

“Previous studies had shown that active behaviors such as locomotion and whisking were associated with a reduction in low-frequency rhythmic activity”

What the sources say

• Not checked yetcites Bennett et al., 2013 source
• Not checked yetcites Crochet and Petersen, 2006
• Not checked yetcites Niell and Stryker, 2010

In the paper

“In short, locomotion and whisking require arousal, but arousal does not necessitate movement”

In the paper

“Interestingly, the initiation of locomotion is preceded by a substantial increase in pupil diameter (Figures 2–4), concurrent with the reduction of low-frequency cortical local field potential synchronization and reduced hippocampal sharp wave and ripple oscillations.”

What the sources say

• Not checked yetcites McGinley et al., 2015 source
• Not checked yetcites Reimer et al., 2014 source
• Not checked yetcites Vinck et al., 2015 source

In the paper

“This suggests that motor processes themselves may also regulate low-frequency synchronization in sensory cortex (Schneider et al., 2014; Zagha et al., 2013) or that states associated with constricting and dilating pupils are distinct, even at the same pupil diameter”

What the sources say

• Not checked yetcites Schneider et al., 2014 source
• Not checked yetcites Zagha et al., 2013 source
• Not checked yetcites Reimer et al., 2014 source

In the paper

“However, in contrast with the increase in neuronal activity period prior to movement, air puff-induced arousal elicits an average decrease in the discharge rate of many cortical neurons.”

What the sources say

• Not checked yetcites Vinck et al., 2015 source

In the paper

“Application of the same arousing stimulus during locomotion, when average neuronal activity is elevated, does not result in a suppression of firing, whereas a transition to locomotion that occurs following induced arousal results in an increase in neuronal discharge”

What the sources say

• Not checked yetcites Vinck et al., 2015 source

In the paper

“The variety and speed of transitions between these states and the ability to manipulate the probability of certain states by varying the timing of the experiments relative to the light cycle make mice a useful species for further investigation along these lines.”

In the paper

“The length of sleep or active periods and the rate of transition between these depends on time relative to the light cycle, with the frequency and duration of bouts of exploratory activity being much greater at the beginning, than the ending, of the active period (lights off).”

What the sources say

• Not checked yetcites Van Twyver, 1969 source

In the paper

“As described above, even in the quiescent state devoid of overt movements, pupil dilation is associated with suppression of low-frequency, and enhancement of gamma-frequency, cortical network activities that can occur as either a rapid switching (Figure 2A) or as a graded and continuous change”

What the sources say

• Not checked yetcites McGinley et al., 2015 source
• Not checked yetcites Reimer et al., 2014 source
• Not checked yetcites Vinck et al., 2015 source

In the paper

“eliciting an increase in arousal through the delivery of an air puff to a quiescent mouse results in a significant increase in pupil diameter and strong suppression of slow rhythmic activity”

What the sources say

• Not checked yetcites Vinck et al., 2015 source

In the paper

“In general, free ranging mice exhibit over 100 transitions between sleep and wakefulness per 24 hour period, with the average sleep or waking period lasting <10 minutes”

What the sources say

• Not checked yetcites Van Twyver, 1969 source

In the paper

“During the period of movement (whisking or locomotion), neurons in somatosensory, visual, motor, and auditory cortex maintain an elevated firing rate, the degree of which varies across cell types.”

What the sources say

• Not checked yetcites Beloozerova et al., 2003 source
• Not checked yetcites McGinley et al., 2015 source

In the paper

“In rodents, brief (seconds) periods of 6–10 Hz thalamocortical oscillations known as high voltage spindles can appear in the quiet resting state and are enhanced by the cessation of locomotion”

What the sources say

• Not checked yetcites Jando et al., 1995 source

In the paper

“Many non-sensory factors affect sensory processing, including behavioral state, motor activity and cross-modal influences (Gur et al., 1997), and their effects may collectively promote response variability (Ecker and Tolias, 2014; Goris et al., 2014; I-Chun et al., 2015).”

What the sources say

• Not checked yetcites Gur et al., 1997 source
• Not checked yetcites Ecker and Tolias, 2014
• Not checked yetcites Goris et al., 2014 source

In the paper

“Behavioral state is an important determinant of both the temporal precision of sensory responses and gamma-band synchronization.”

What the sources say

• Not checked yetcites Lee et al., 2014 source
• Not checked yetcites McGinley et al., 2015 source
• Not checked yetcites Vinck et al., 2015 source

In the paper

“In mouse visual cortex, the S/N is small at low arousal levels, and increases at high arousal levels and during locomotion”

What the sources say

• Not checked yetcites Bennett et al., 2013 source
• Not checked yetcites Niell and Stryker, 2010
• Not checked yetcites Vinck et al., 2015 source

In the paper

“In cat V1, the signal-to-noise ratio (S/N; evoked/spontaneous activity) increases during waking versus sleeping, due in part to increases in spontaneous activity during sleep”

What the sources say

• Not checked yetcites Livingstone and Hubel, 1981

In the paper

“In contrast, in auditory cortex, the S/N peaks at intermediate arousal levels and may decrease strongly at high arousal levels and during locomotion”

What the sources say

• Not checked yetcites McGinley et al., 2015 source

In the paper

“Spontaneous or causally induced increases in arousal are associated with a monotonic increase in gamma-band synchronization both in terms of local field potential and relative membrane potential power (Lee et al., 2014; Lima et al., 2011; McGinley et al., 2015; Reimer et al., 2014; Vinck et al., 2015), and spike-local field potential phase locking”

What the sources say

• Not checked yetcites Lee et al., 2014 source
• Not checked yetcites McGinley et al., 2015 source
• Not checked yetcites Vinck et al., 2015 source

In the paper

“Changes in arousal result in marked multiplicative gain modulation of auditory cortical responses, with the largest responses being evoked at intermediate levels of arousal”

What the sources say

• Not checked yetcites McGinley et al., 2015 source

In the paper

“Several theoretical and empirical studies have suggested that one important temporal feature of cortical sensory processing is gamma-band (30–80 Hz) synchronization, which is beneficial for information coding (Vinck et al., 2010; Womelsdorf et al., 2012), inter-areal transmission (Bosman et al., 2012; Womelsdorf et al., 2007) and behavioral performance”

What the sources say

• Not checked yetcites Vinck et al., 2010 source
• Not checked yetcites Womelsdorf et al., 2012 source
• Not checked yetcites Bosman et al., 2012 source

In the paper

“Pupil dilations during quiet wakefulness also correspond to an increase in visual responsiveness along with an enhancement of selectivity”

What the sources say

• Not checked yetcites Vinck et al., 2015 source

In the paper

“In V1, locomotion causes both multiplicative and additive enhancements of responses to drifting gratings”

What the sources say

• Not checked yetcites Bennett et al., 2013 source
• Not checked yetcites Niell and Stryker, 2010
• Not checked yetcites Polack et al., 2013 source

In the paper

“The degradation of sensory responses by slow wave sleep and anesthesia, in comparison to waking, are well known”

What the sources say

• Not checked yetcites Livingstone and Hubel, 1981
• Not checked yetcites Marguet and Harris, 2011

In the paper

“Together, these findings across waking states show substantial modulation of sensory response magnitude that can be well predicted by variations in arousal.”

In the paper

“In contrast, in states with prominent low frequencies in cortical network activity, sensory stimuli may trigger responses that are either inappropriately weak or strong, and which do not optimally represent the spatiotemporal features of the stimulus”

What the sources say

• Not checked yetcites Hasenstaub et al., 2007 source
• Not checked yetcites Livingstone and Hubel, 1981
• Not checked yetcites Massimini et al., 2005 source

In the paper

“Neuronal variability in firing rates is particularly high during anesthesia, possibly as a result of enhanced slow fluctuations (Arieli et al., 1996; Ecker and Tolias, 2014; Goard and Dan, 2009; Goris et al., 2014; Hasenstaub et al., 2007; I-Chun et al., 2015; Marguet and Harris, 2011; Scholvinck et al., 2015; Zagha et al., 2013).”

What the sources say

• Not checked yetcites Arieli et al., 1996 source
• Not checked yetcites Ecker and Tolias, 2014
• Not checked yetcites Goard and Dan, 2009

In the paper

“Thus, a precise analysis of behavioral state seems to explain considerable variability in noise correlations, and poor control or knowledge of behavioral state can lead to artificial inflation.”

In the paper

“These findings reveal a strong convergence between the effects of attention and global arousal and suggest that the underlying cellular/network mechanisms may be related.”

In the paper

“Moderate increases in LC activity enhance the cortical S/N ratio and set the conditions for optimal neural and behavioral performance, but further increasing LC discharge rates to high levels can have detrimental effects (Aston-Jones and Cohen, 2005).”

What the sources say

• Not checked yetcites Aston-Jones and Cohen, 2005 source

In the paper

“(however, in another recent study the presence of slow oscillatory events in the somatosensory cortex was not detrimental to the performance of a touch detection task, although the strength of stimulus used was supramaximal at all arousal levels) (Sachidhanandam et al., 2013).”

What the sources say

• Not checked yetcites Sachidhanandam et al., 2013 source

In the paper

“increases the S/N and both spontaneous and evoked firing rates (Luck et al., 1997; McAdams and Maunsell, 1999b; Reynolds et al., 1999; Reynolds and Desimone, 1999)”

What the sources say

• Not checked yetcites Luck et al., 1997 source
• Not checked yetcites McAdams and Maunsell, 1999b
• Not checked yetcites Reynolds et al., 1999

In the paper

“Activation of receptors for these neuromodulators at intermediate levels may enhance performance on PFC dependent tasks, whereas further increases may result in a decrement in behavioral performance and reduced neural representation of that performance in the PFC (reviewed in (Arnsten, 2009; Arnsten et al., 2012)).”

What the sources say

• Not checked yetcites Arnsten, 2009 source
• Not checked yetcites Arnsten et al., 2012 source

In the paper

“Locomotion increases response amplitude and decreases response variability in V1 (Figure 5) (Erisken et al., 2014)”

What the sources say

• Not checked yetcites Erisken et al., 2014 source

In the paper

“More than a century ago, Robert Yerkes and John Dodson (Yerkes and Dodson, 1908) proposed that increases in arousal/stress from low to moderate levels can facilitate performance on a difficult behavioral task, whereas further increases from moderate to severe can impair performance.”

What the sources say

• Not checked yetcites Yerkes and Dodson, 1908 source

In the paper

“The more similar the pattern of ECoG activity to the average of all trials, the better the performance on the visual detection task, with significant decrements in performance when the ECoG activity deviated in either direction from average (He and Zempel, 2013).”

What the sources say

• Not checked yetcites He and Zempel, 2013

In the paper

“Importantly, the performance of mice on this auditory detection task was highly state dependent, with maximal hit rate, shortest lick latency, maximal discrimination, and least behavioral bias all occurring at intermediate pupil diameters (Figure 7C).”

What the sources say

• Not checked yetcites McGinley et al., 2015 source

In the paper

“Increases in arousal from low to intermediate, as indicated by increases in pupil diameter from small to medium, were associated with a large increase in task performance, while further increases in pupil diameter from intermediate to large were associated with a strong decrement in performance, whether or not the animal was walking at these large pupil diameters (Figure 7C).”

What the sources say

• Not checked yetcites McGinley et al., 2015 source

In the paper

“The locus coeruleus provides the source of noradrenergic, and the basal forebrain the source of cholinergic, innervation of the cerebral cortex.”

What the sources say

• Not checked yetcites Saper et al., 2010 source
• Not checked yetcites Steriade and McCarley, 2005

In the paper

“It is likely that cell type, laminar location, behavioral context, and perhaps region of cortex are important variables (Beloozerova et al., 2003; Gentet et al., 2010; Reimer et al., 2014).”

What the sources say

• Not checked yetcites Beloozerova et al., 2003 source
• Not checked yetcites Gentet et al., 2010 source
• Not checked yetcites Reimer et al., 2014 source

In the paper

“Locomotion, as we have mentioned, is associated with a suppression of slow rhythmic activity in cortical networks, a depolarization of cortical neurons closer to action potential threshold, and enhanced visually evoked responses (Bennett et al., 2013; Polack et al., 2013; Reimer et al., 2014).”

What the sources say

• Not checked yetcites Bennett et al., 2013 source
• Not checked yetcites Polack et al., 2013 source
• Not checked yetcites Reimer et al., 2014 source

In the paper

“Effects that are consistent with a role in arousal of pyramidal cell networks include depolarization of cortical neurons through the reduction of a variety of membrane K+ currents (McCormick, 1992), modulation of the h-current (Wang et al., 2007), which controls neuronal and dendritic excitability (Magee, 2000), and control of synaptic transmission, through the modulation of presynaptic terminals”

What the sources say

• Not checked yetcites McCormick, 1992 source
• Not checked yetcites Wang et al., 2007 source
• Not checked yetcites Magee, 2000 source

In the paper

“Interestingly, locomotion, as a sub-state of hyper-arousal, was associated with a strong decrease in behavioral performance, in comparison to intermediate arousal levels, which always occurred during stillness.”

What the sources say

• Not checked yetcites McGinley et al., 2015 source

In the paper

“Not tracking the beginning and ending points of changes in arousal may contribute significantly to the wide variations observed between studies in the effects of arousal on spontaneous cortical discharge rates.”

In the paper

“All three measures exhibited an inverted U relationship with arousal, with the largest, most reliable, and highest S/N ratio responses occurring at the same intermediate pupil diameters that revealed optimal performance on the auditory tone-in-complex sound detection task (Figure 7).”

What the sources say

• Not checked yetcites McGinley et al., 2015 source

In the paper

“These results indicate that arousal level robustly influences behavioral performance, and this influence can take the form of an inverted U in this task, as predicted by the curvilinear component of the Yerkes-Dodson relationship (Figure 7C).”

In the paper

“In an auditory odd-ball task, response latency upon detection of the correct stimulus was shortest at mid-pupil diameters in human subjects and the P3 evoked potential was also maximal at this level of arousal, resulting in U (latency) and inverted-U (evoked cortical field potential P3 amplitude) relationships with pupil-indexed arousal (Murphy et al., 2011).”

What the sources say

• Not checked yetcites Murphy et al., 2011 source

In the paper

“Through the modulation of ionic currents, the release of norephinephrine or acetylcholine can not only control the membrane potential and excitability of cortical neurons, but also strongly suppress the generation of slow oscillations.”

What the sources say

• Not checked yetcites McCormick, 1992 source

In the paper

“Stimulation of the locus coeruleus can markedly enhance auditory cortical responses and increase learning induced plasticity (Martins and Froemke, 2015).”

What the sources say

• Not checked yetcites Martins and Froemke, 2015 source

In the paper

“In cortical networks, nicotinic and 5HT3A receptors are often (but not exclusively) located on particular subpopulations of GABAergic interneurons (Fu et al., 2014; Griguoli and Cherubini, 2012; Jakab and Goldman-Rakic, 2000) and may contribute to modulation of waking state activities through disinhibition.”

What the sources say

• Not checked yetcites Fu et al., 2014
• Not checked yetcites Griguoli and Cherubini, 2012
• Not checked yetcites Jakab and Goldman-Rakic, 2000

In the paper

“These diverse findings strongly support a prominent role for both the central cholinergic and noradrenergic pathways in the rapid modulation of cortical state.”

In the paper

“Both cholinergic and serotoninergic systems can activate kinetically fast excitatory postsynaptic potentials in postsynaptic targets through nicotinic and 5HT3A receptors, respectively, and the discharges of both cholinergic (e.g. Figure 9C) and serotonergic neurons are strongly modulated by movement (Eggermann et al., 2014; Jacobs and Fornal, 1993) (Reimer, McGinley, McCormick, Tolias, unpub”

What the sources say

• Not checked yetcites Eggermann et al., 2014 source
• Not checked yetcites Jacobs and Fornal, 1993
• Not checked yetcites Reimer et al., unpublished

In the paper

“Such fast actions may be particularly beneficial where rapid modulations in local or long range network processing are required, such as alterations in attention or in motor planning/execution.”

In the paper

“While the pathways that link changes in pupil diameter with arousal are currently unknown, locus coeruleus neurons have been reported to discharge in close relation to pupil diameter on a time scale of tens of seconds (Aston-Jones and Cohen, 2005; Murphy et al., 2014a) and electrical stimulation in the region of the locus coeruleus results in pupil dilation (Liu, Li, Wang, Society for Neuroscience”

What the sources say

• Not checked yetcites Aston-Jones and Cohen, 2005 source
• Not checked yetcites Murphy et al., 2014a
• Not checked yetcites Liu et al., 2014

In the paper

“The locus coeruleus receives synaptic inputs from multiple brain regions, such as the frontal cortex, that may be involved in arousal responses to complex stimuli, including those requiring high level cognition(Aston-Jones and Cohen, 2005).”

What the sources say

• Not checked yetcites Aston-Jones and Cohen, 2005 source

In the paper

“VIP-containing cortical inhibitory interneurons project to both somatostatin (e.g. Martinotti) and parvalbumin (e.g. basket cells) containing interneurons and have an inhibitory action on these cell types (David et al., 2007; Jiang et al., 2013; Lee et al., 2013; Pi et al., 2013).”

What the sources say

• Not checked yetcites David et al., 2007 source
• Not checked yetcites Jiang et al., 2013 source
• Not checked yetcites Lee et al., 2013 source

In the paper

“Interestingly, VIP-containing neurons show rapid depolarization to serotoninergic and cholinergic inputs from subcortical pathways and glutamatergic inputs from higher cortical areas, positioning these interneurons as possible effectors of multiple modulatory inputs.”

What the sources say

• Not checked yetcites Fu et al., 2014
• Not checked yetcites Lee et al., 2013 source
• Not checked yetcites Pi et al., 2013

In the paper

“allow for a more accurate exploration of the neural mechanisms of behavior at all levels, from sensory coding, decision, to motor response”