Nonlinear changes in pupillary attentional orienting responses across the lifespan.

The cognitive aging process is not necessarily linear. Central task-evoked pupillary responses, representing a brainstem-pupil relationship, may vary across the lifespan. Thus we examined, in 75 adults ranging in age from 19 to 86, whether task-evoked pupillary responses to an attention task may serve in as an index of cognitive aging. This is because the locus coeruleus (LC), located in the brainstem, is not only among the earliest sites of degeneration in pathological aging, but also supports both attentional and pupillary behaviors. We assessed brief, task-evoked phasic attentional orienting to behaviorally relevant and irrelevant auditory tones, stimuli known specifically to recruit the LC in the brainstem and evoke pupillary responses. Due to potential nonlinear changes across the lifespan, we used a novel data-driven analysis on 6 dynamic pupillary behaviors on 10% of the data to reveal cut off points that best characterized the three age bands: young (19-41 years old), middle aged (42-68 years old), and older adults (69 + years old). Follow-up analyses on independent data, the remaining 90%, revealed age-related changes such as monotonic decreases in tonic pupillary diameter and dynamic range, along with curvilinear phasic pupillary responses to the behaviorally relevant target events, increasing in the middle-aged group and then decreasing in the older group. Additionally, the older group showed decreased differentiation of pupillary responses between target and distractor events. This pattern is consistent with potential compensatory LC activity in midlife that is diminished in old age, resulting in decreased adaptive gain. Beyond regulating responses to light, pupillary dynamics reveal a nonlinear capacity for neurally mediated gain across the lifespan, thus providing evidence in support of the LC adaptive gain hypothesis.

Locus coeruleus neuromelanin accumulation and dissipation across the lifespan.

The pigment neuromelanin, produced in the locus coeruleus (LC) as a byproduct of catecholamine synthesis, gives the "blue spot" its name, and both identifies LC neurons and is thought to play an important yet complex role in normal and pathological aging. Using neuromelanin-sensitive T1-weighted turbo spin echo MRI scans we characterized volume and neuromelanin signal intensity in the LC of 96 participants between the ages of 19 and 86. Although LC volume did not change significantly throughout the lifespan, LC neuromelanin signal intensity increased from early adulthood, peaked around age 60 and precipitously declined thereafter. Neuromelanin intensity was greater in the caudal relative to rostral extent and in women relative to men. With regard to function, rostral LC neuromelanin intensity was associated with fluid cognition in older adults (60+) only in those above the 50th percentile of cognitive ability for age. The gradual accumulation of LC neuromelanin across the lifespan, its sudden dissipation in later life, and relation to preserved cognitive function, is consistent with its complex role in normal and pathological aging.

Attention-dependent coupling with forebrain and brainstem neuromodulatory nuclei changes across the lifespan.

Attentional states continuously reflect the predictability and uncertainty in one's environment having important consequences for learning and memory. Beyond well known cortical contributions, rapid shifts in attention are hypothesized to also originate from deep nuclei, such as the basal forebrain (BF) and locus coeruleus (LC) neuromodulatory systems. These systems are also the first to change with aging. Here we characterized the interplay between these systems and their regulation of afferent targets - the hippocampus (HPC) and posterior cingulate cortex (PCC) - across the lifespan. To examine the role of attentional salience on task-dependent functional connectivity, we used a target-distractor go/no go task presented during functional MRI. In younger adults, BF coupling with the HPC, and LC coupling with the PCC, increased with behavioral relevance (targets vs distractors). Although the strength and presence of significant regional coupling changed in middle age, the most striking change in network connectivity was in old age, such that in older adults BF and LC coupling with their cortical afferents was largely absent and replaced by stronger interconnectivity between LC-BF nuclei. Overall rapid changes in attention related to behavioral relevance revealed distinct roles of subcortical neuromodulatory systems. The pronounced changes in functional network architecture across the lifespan suggest a decrease in these distinct roles, with deafferentation of cholinergic and noradrenergic systems associated with a shift towards mutual support during attention guided to external stimuli.

Wrinkles in subsecond time perception are synchronized to the heart.

The role of the heart in the experience of time has been long theorized but empirical evidence is scarce. Here, we examined the interaction between fine-grained cardiac dynamics and the momentary experience of subsecond intervals. Participants performed a temporal bisection task for brief tones (80-188 ms) synchronized with the heart. We developed a cardiac Drift-Diffusion Model (cDDM) that embedded contemporaneous heart rate dynamics into the temporal decision model. Results revealed the existence of temporal wrinkles-dilation or contraction of short intervals-in synchrony with cardiac dynamics. A lower prestimulus heart rate was associated with an initial bias in encoding the millisecond-level stimulus duration as longer, consistent with facilitation of sensory intake. Concurrently, a higher prestimulus heart rate aided more consistent and faster temporal judgments through more efficient evidence accumulation. Additionally, a higher speed of poststimulus cardiac deceleration, a bodily marker of attention, was associated with a greater accumulation of sensory temporal evidence in the cDDM. These findings suggest a unique role of cardiac dynamics in the momentary experience of time. Our cDDM framework opens a new methodological avenue for investigating the role of the heart in time perception and perceptual judgment.

Interaction of cholinergic disruption and age on cognitive flexibility in rats.

Healthy aging is associated with a functional reduction of the basal forebrain (BF) system that supplies the neurochemical acetylcholine (ACh) to the cortex, and concomitant challenges to cognition. It remains unclear how aging and ACh loss interact to shape cognition in the aging brain. We used a proactive interference (PI) odor discrimination task, shown to depend on the BF in young adults, wherein rats acquired new associations that conflicted with past learning or associations that did not conflict. This manipulation allowed independent assessment of encoding alone vs. encoding in the face of interference. Adult (9.8 ± 1.3 months) or aged male Long-Evans rats (20.7 ± 0.5 months) completed the PI task with systemic administration of a muscarinic cholinergic antagonist, scopolamine, or a pharmacological control. Aged rats were less able to resolve PI than adult rats. Moreover, while scopolamine reduced efficient PI resolution in adult rats, this cholinergic antagonism had no additional effect on aged rat performance, counter to our expectation that scopolamine would further increase perseveration in the aged group. Scopolamine did not impair encoding of non-interfering associations regardless of age. These data suggest that natural aging changes the effect of cholinergic pharmacology on encoding efficiency when past learning interferes.

Face-to-face learning enhances the social transmission of information.

Learning from others provides the foundation for culture and the advancement of knowledge. Learning a new visuospatial skill from others represents a specific challenge-overcoming differences in perspective so that we understand what someone is doing and why they are doing it. The "what" of visuospatial learning is thought to be easiest from a shared 0° first-person perspective and most difficult from a 180° third-person perspective. However, the visual disparity at 180° promotes face-to-face interaction, which may enhance learning by scaffolding social perspective taking, the "why" of visuospatial learning. We tested these potentially conflicting hypotheses in child and young adult learners. Thirty-six children (4-6 years) and 57 young adults (18-27 years) observed a live model open a puzzle box from a first-person (0°) or third-person (90° or 180°) perspective. The puzzle box had multiple solutions, only one of which was modelled, which allowed for the assessment of imitation and goal emulation. Participants had three attempts to open the puzzle box from the model's perspective. While first-person (0°) observation increased imitation relative to a 180° third-person perspective, the 180° observers opened the puzzle box most readily (i.e., fastest). Although both age groups were excellent imitators and able to take the model's perspective, adults were more faithful imitators, and children were more likely to innovate a new solution. A shared visual perspective increased imitation, but a shared mental perspective promoted goal achievement and the social transmission of innovation. "Perfection of means and confusion of goals-in my opinion-seem to characterize our age" Einstein (1973) pg 337, Ideas and Opinions.

Differential color tuning of the mesolimbic reward system.

Visual wavelengths are not only associated with the subjective experience of color but also have long been thought to regulate affect. Here we examined the attracting rewarding properties of opposite ends of the wavelength spectrum, as well as their individual variation. As reward is multifaceted, we sought convergent evidence from subjective and objective behavioral and attentional indices, as well as its neural reward system bases. On average, short (blue) relative to long (red) wavelengths were judged subjectively more pleasant and had objectively greater behavioral and attentional salience, regulating speed of simple color discriminations and perception of temporal order. Consistent with reward, these color effects were magnified following monetary reinforcement. Pronounced individual differences in color effects were related to reward but not punishment sensitivity, with blue relative to red preference associated with high relative to low reward sensitivity. An fMRI study revealed these individual differences were supported by color-dependent functional coupling between the visual cortices and mesolimbic reward circuitry. Our findings reveal the reward bases of color, demonstrating color is a potent regulator of perception, action, and neural dynamics.

Attention and cardiac phase boost judgments of trust.

Fluctuations in mental and bodily states have both been shown to be associated with negative affective experience. Here we examined how momentary fluctuations in attentional and cardiac states combine to regulate the perception of positive social value. Faces varying in trustworthiness were presented during a go/no-go letter target discrimination task synchronized with systolic or diastolic cardiac phase. Go trials lead to an attentional boosting of perceived trust on high trust and ambiguous neutral faces, suggesting attention both boosted existing and generated positive social value. Cardiac phase during face presentation interacted with attentional boosting of trust, enhancing high trust faces specifically during relaxed diastolic cardiac states. Confidence judgments revealed that attentional trust boosting, and its cardiac modulation, did not reflect altered perceptual or response fluency. These results provide evidence for how moment-to moment fluctuations in top-down mental and bottom-up bodily inputs combine to enhance a priori and generate de novo positive social value.

Yellow is for safety: perceptual and affective perspectives.

Is there a link between color and safety? Yellow is often used in safety contexts. Using the Singapore accident record datasets, Ho et al. provided evidence that yellow taxis have fewer accidents than blue taxis (Ho et al. in Proc Natl Acad Sci 114(12):3074-3078, 2017). Does yellow differentially influence attention and action and if so is this related to purely visual or affective factors? Here, we examined the visual priority of yellow relative to luminance matched colors at opposing ends of the wavelength spectrum (i.e., red and blue), using a temporal order judgment task, between color pairs. Despite being matched in arousal, when yellow and blue were pitted against each other, yellow was consistently seen as occurring first, even when objectively appearing second at short stimulus onset asynchronies. Despite being matched in valence, yellow again showed a larger temporal priority when it was pitted against red. Yellow temporal priority bias was modulated by individual differences in regulatory focus, highlighting a potential affective-motivational origin. These results support that yellow is a safety color, having a temporal advantage, and further evidence that colors have special influences on cognition, perception and behavior.

Differential temporal salience of earning and saving.

People are often characterized as poor savers. Here we examined whether cues associated with earning and saving have differential salience for attention and action. We first modeled earning and saving after positive and negative variants of monetary reinforcement, i.e., gains versus avoiding loss. Despite their equivalent absolute magnitude in a monetary incentive task, colors predicting saving were judged to appear after those that predicted earning in a temporal-order judgment task. This saving posteriority effect also occurred when savings were framed as earnings that come slightly later. Colors predicting savings, whether they acquired either negative or positive value, persisted in their posteriority. An attentional asymmetry away from money-saved relative to money-earned, potentially contributes to decreased everyday salience and future wealth.

Segregation of the human basal forebrain using resting state functional MRI.

The basal forebrain (BF) is poised to play an important neuromodulatory role in brain regions important to cognition due to its broad projections and complex neurochemistry. While significant in vivo work has been done to elaborate BF function in nonhuman rodents and primates, comparatively limited work has examined the in vivo function of the human BF. In the current study we used multi-echo resting state functional magnetic resonance imaging (rs-fMRI) from 100 young adults (18-34 years) to assess the potential segregation of human BF nuclei as well as their associated projections. Multi-echo processing provided significant gains in SNR throughout the brain as compared to traditional single-echo processing, with some of the largest increases observed in the BF. Bottom-up clustering of voxel-wise BF functional connectivity maps yielded adjacent functional clusters within the BF that closely aligned with the distinct, hypothesized nuclei important to cognition: the nucleus basalis of Meynert (NBM) and the medial septum/diagonal band of Broca (MS/DB). Examining their separate functional connections, the NBM and MS/DB revealed distinct projection patterns, suggesting a conservation of nuclei-specific functional connectivity with homologous regions known to be anatomically innervated by the BF. Specifically, the NBM demonstrated coupling with a widespread cortical network as well as the amygdala, whereas the MS/DB revealed coupling with a more circumscribed network, including the orbitofrontal cortex and hippocampal complex. Collectively, these in vivo rs-fMRI data demonstrate that the human BF nuclei support distinct aspects of resting-state functional networks, suggesting that the human BF may be a neuromodulatory hub important for orchestrating network dynamics.

Cholinergic Modulation of Frontoparietal Cortical Network Dynamics Supporting Supramodal Attention.

A critical function of attention is to support a state of readiness to enhance stimulus detection, independent of stimulus modality. The nucleus basalis magnocellularis (NBM) is the major source of the neurochemical acetylcholine (ACh) for frontoparietal cortical networks thought to support attention. We examined a potential supramodal role of ACh in a frontoparietal cortical attentional network supporting target detection. We recorded local field potentials (LFPs) in the prelimbic frontal cortex (PFC) and the posterior parietal cortex (PPC) to assess whether ACh contributed to a state of readiness to alert rats to an impending presentation of visual or olfactory targets in one of five locations. Twenty male Long-Evans rats underwent training and then lesions of the NBM using the selective cholinergic immunotoxin 192 IgG-saporin (0.3 µg/µl; ACh-NBM-lesion) to reduce cholinergic afferentation of the cortical mantle. Postsurgery, ACh-NBM-lesioned rats had less correct responses and more omissions than sham-lesioned rats, which changed parametrically as we increased the attentional demands of the task with decreased target duration. This parametric deficit was found equally for both sensory targets. Accurate detection of visual and olfactory targets was associated specifically with increased LFP coherence, in the beta range, between the PFC and PPC, and with increased beta power in the PPC before the target's appearance in sham-lesioned rats. Readiness-associated changes in brain activity and visual and olfactory target detection were attenuated in the ACh-NBM-lesioned group. Accordingly, ACh may support supramodal attention via modulating activity in a frontoparietal cortical network, orchestrating a state of readiness to enhance target detection.SIGNIFICANCE STATEMENT We examined whether the neurochemical acetylcholine (ACh) contributes to a state of readiness for target detection, by engaging frontoparietal cortical attentional networks independent of modality. We show that ACh supported alerting attention to an impending presentation of either visual or olfactory targets. Using local field potentials, enhanced stimulus detection was associated with an anticipatory increase in power in the beta oscillation range before the target's appearance within the posterior parietal cortex (PPC) as well as increased synchrony, also in beta, between the prefrontal cortex and PPC. These readiness-associated changes in brain activity and behavior were attenuated in rats with reduced cortical ACh. Thus, ACh may act, in a supramodal manner, to prepare frontoparietal cortical attentional networks for target detection.

Will Analytics Suppress a Diversity of Ideas in Psychological Science?

In this article, I suggest that an overreliance on analytics to assess faculty productivity and the diffusion of ideas may inadvertently suppress innovation. Even when these productivity-diffusion metrics are used to promote an individual's work, the use of such external guideposts may bias scientific choices and curb a psychological scientist's earnest inclination to synthesize or take scientific risks. Analytics are not inert but can change the path and progress of science itself, potentially reducing the diversity of ideas in psychological science. This potential harm may most affect new scholars at the beginning of their independent research careers.

Distinguishing attentional gain and tuning in young and older adults.

Here we examined with functional magnetic resonance imaging (fMRI) whether advanced age affects 2 mechanisms of attention that are widely thought to enhance signal processing in the sensory neocortex: gain and tuning. Healthy young and older adults discriminated faces under varying levels of object competition while fMRI was acquired. In young adults, cortical response magnitude to attended faces was maintained despite increasing competition, consistent with gain. Cortical response selectivity, indexed from repetition suppression, also increased only for attended faces despite increasing competition, consistent with tuning. Older adults exhibited intact gain, but altered tuning, with extrastriate cortical tuning determined by object salience rather than attention. Moreover, the magnitude of this susceptibility to stimulus-driven processing was associated with a redistribution of attention-driven competitive processes to the frontal cortices. These data indicate that although both gain and tuning are modulated by increased perceptual competition, they are functionally dissociable in the extrastriate cortices, exhibit differential susceptibility to advanced aging, and spare the frontal cortices a considerable processing burden through early selection.

Cholinergic contributions to supramodal attentional processes in rats.

Cholinergic neurotransmission has been shown to play an important role in modulating attentional processing of visual stimuli. However, it is not yet clear whether the neurochemical acetylcholine (ACh) is necessary exclusively for visual attention, or if it also contributes to attentional functions through some modality-independent (supramodal) mechanism. To answer this question, we examined the effects of reduced cortical cholinergic afferentation on both a traditional visual and a novel olfactory five-choice serial reaction time task (5-CSRTT), the benchmark rodent test of sustained attention in rats. Following the successful acquisition of both modalities of the task, the rats underwent either a cholinergic immunotoxic- or sham-lesion surgery of the nucleus basalis magnocellularis (NBM), the basal forebrain nuclei that provide the majority of neocortical ACh. Reduced cholinergic afferentation to the neocortex was induced by bilaterally infusing the cholinergic immunotoxin 192 IgG-saporin into the NBM. After surgery, ACh-NBM-lesioned rats performed comparably to sham-lesioned rats under the conditions of low attentional demand, but displayed behavioral decrements relative to the sham-lesioned rats when the attentional demands of the task were increased. Moreover, this decrement in attentional functioning correlated significantly with the number of choline acetyltransferase-immunoreactive cells in the NBM. Importantly, the nature of this behavioral decrement was identical in the visual and olfactory 5-CSRTTs. Together, these data suggest the presence of a supramodal attentional modulatory cortical network whose activity is dependent on cholinergic innervation from the NBM.

Impaired visual search in rats reveals cholinergic contributions to feature binding in visuospatial attention.

The visual search task established the feature integration theory of attention in humans and measures visuospatial attentional contributions to feature binding. We recently demonstrated that the neuromodulator acetylcholine (ACh), from the nucleus basalis magnocellularis (NBM), supports the attentional processes required for feature binding using a rat digging-based task. Additional research has demonstrated cholinergic contributions from the NBM to visuospatial attention in rats. Here, we combined these lines of evidence and employed visual search in rats to examine whether cortical cholinergic input supports visuospatial attention specifically for feature binding. We trained 18 male Long-Evans rats to perform visual search using touch screen-equipped operant chambers. Sessions comprised Feature Search (no feature binding required) and Conjunctive Search (feature binding required) trials using multiple stimulus set sizes. Following acquisition of visual search, 8 rats received bilateral NBM lesions using 192 IgG-saporin to selectively reduce cholinergic afferentation of the neocortex, which we hypothesized would selectively disrupt the visuospatial attentional processes needed for efficient conjunctive visual search. As expected, relative to sham-lesioned rats, ACh-NBM-lesioned rats took significantly longer to locate the target stimulus on Conjunctive Search, but not Feature Search trials, thus demonstrating that cholinergic contributions to visuospatial attention are important for feature binding in rats.

Failing to ignore: paradoxical neural effects of perceptual load on early attentional selection in normal aging.

We examined visual selective attention under perceptual load--simultaneous presentation of task-relevant and -irrelevant information--in healthy young and older adult human participants to determine whether age differences are observable at early stages of selection in the visual cortices. Participants viewed 50/50 superimposed face/place images and judged whether the faces were male or female, rendering places perceptible but task-irrelevant. Each stimulus was repeated, allowing us to index dynamic stimulus-driven competition from places. Consistent with intact early selection in young adults, we observed no adaptation to unattended places in parahippocampal place area (PPA) and significant adaptation to attended faces in fusiform face area (FFA). Older adults, however, exhibited both PPA adaptation to places and weak FFA adaptation to faces. We also probed participants' associative recognition for face-place pairs post-task. Older adults with better place recognition memory scores were found to exhibit both the largest magnitudes of PPA adaptation and the smallest magnitudes of FFA adaptation on the attention task. In a control study, we removed the competing perceptual information to decrease perceptual load. These data revealed that the initial age-related impairments in selective attention were not due to a general decline in visual cortical selectivity; both young and older adults exhibited robust FFA adaptation and neither group exhibited PPA adaptation to repeated faces. Accordingly, distracting information does not merely interfere with attended input in older adults, but is co-encoded along with the contents of attended input, to the extent that this information can subsequently be recovered from recognition memory.

Evidence for intact memory-guided attention in school-aged children.

Visual scenes contain many statistical regularities such as the likely identity and location of objects that are present; with experience, such regularities can be encoded and can ultimately facilitate the deployment of spatial attention to important locations. Memory-guided attention has been extensively examined in adults with the 'contextual cueing' paradigm and has been linked to specific neural substrates - a medial temporal lobe (MTL)-frontoparietal network. However, it currently remains unknown when this ability comes 'online' during development. Thus, we examined the performance of school-aged children on an age-appropriate version of the contextual cueing paradigm. Children searched for a target fish among distractor fish in new displays and in 'old' displays on a touchscreen computer. Old displays repeated across blocks of trials and thus provided an opportunity for prior experience with the invariant configuration of the stimuli to guide attentional deployment. We found that over time children searched old displays significantly faster than new displays, thus revealing intact memory-guided attention and presumed function of an MTL-frontoparietal network in 5- to 9-year-olds. More generally, our findings suggest that children are remarkably sensitive to the inherent structure of their visual environment and this enables attentional deployment to become more efficient with experience.

Opposing influences of affective state valence on visual cortical encoding.

Positive and negative emotional states are thought to have originated from fundamentally opposing approach and avoidance behaviors. Furthermore, affective valence has been hypothesized to exert opposing biases in cognitive control. Here we examined with functional magnetic resonance imaging whether the opposing influences of positive and negative states extend to perceptual encoding in the visual cortices. Based on prior behavioral research, we hypothesized that positive states would broaden and negative states would narrow visual field of view (FOV). Positive, neutral, and negative states were induced on alternating blocks. To index FOV, observers then viewed brief presentations (300 ms) of face/place concentric center/surround stimuli on interleaved blocks. Central faces were attended, rendering the place surrounds unattended. As face and place information was presented at different visual eccentricities, our physiological metric of FOV was a valence-dependent modulation of place processing in the parahippocampal place area (PPA). Consistent with our hypotheses, positive affective states increased and negative states decreased PPA response to novel places as well as adaptation to repeated places. Individual differences in self-reported positive and negative affect correlated inversely with PPA encoding of peripheral places, as well as with activation in the mesocortical prefrontal cortex and amygdala. Psychophysiological interaction analyses further demonstrated that valence-dependent responses in the PPA arose from opponent coupling with extrafoveal regions of the primary visual cortex during positive and negative states. These findings collectively suggest that affective valence differentially biases gating of early visual inputs, fundamentally altering the scope of perceptual encoding.

Cholinergic deafferentation of the neocortex using 192 IgG-saporin impairs feature binding in rats.

The binding problem refers to the fundamental challenge of the CNS to integrate sensory information registered by distinct brain regions to form a unified neural representation of a stimulus. Although the human cognitive literature has established that attentional processes in frontoparietal cortices support feature binding, the neurochemical and specific downstream neuroanatomical contributions to feature binding remain unknown. Using systemic pharmacology in rats, it has been shown that the neuromodulator acetylcholine is essential for feature binding at encoding, but the neural source of such critical cholinergic neurotransmission has yet to be identified. Cholinergic efferents from the nucleus basalis magnocellularis (NBM) of the basal forebrain provide the majority of the cholinergic input to the neocortex. Accordingly, it was hypothesized that the NBM is the neural source that provides the critical neuromodulatory support for feature binding. To test this hypothesis, rats received bilateral 192 IgG-saporin lesions of the NBM, and their feature binding performance was tested using a forced-choice digging paradigm. Relative to sham-lesioned rats, NBM-lesioned rats were significantly impaired at acquiring a crossmodal feature conjunction (FC) stimulus set that required feature binding, whereas their ability to retrieve an FC stimulus set and to acquire two crossmodal feature singleton stimulus sets, one of greater difficulty than the other but neither requiring feature binding, remained intact. These behavioral findings, along with histological analyses demonstrating positive relationships between feature-binding acquisition and markers of cholinergic activity in frontoparietal regions, reveal the importance of neocortical cholinergic input from the NBM to feature binding at encoding.