Affine image registration of arterial spin labeling MRI using deep learning networks.

Convolutional neural networks (CNN) have demonstrated good accuracy and speed in spatially registering high signal-to-noise ratio (SNR) structural magnetic resonance imaging (sMRI) images. However, some functional magnetic resonance imaging (fMRI) images, e.g., those acquired from arterial spin labeling (ASL) perfusion fMRI, are of intrinsically low SNR and therefore the quality of registering ASL images using CNN is not clear. In this work, we aimed to explore the feasibility of a CNN-based affine registration network (ARN) for registration of low-SNR three-dimensional ASL perfusion image time series and compare its performance with that from the state-of-the-art statistical parametric mapping (SPM) algorithm. The six affine parameters were learned from the ARN using both simulated motion and real acquisitions from ASL perfusion fMRI data and the registered images were generated by applying the transformation derived from the affine parameters. The speed and registration accuracy were compared between ARN and SPM. Several independent datasets, including meditation study (10 subjects × 2), bipolar disorder study (26 controls, 19 bipolar disorder subjects), and aging study (27 young subjects, 33 older subjects), were used to validate the generality of the trained ARN model. The ARN method achieves superior image affine registration accuracy (total translation/total rotation errors of ARN vs. SPM: 1.17 mm/1.23° vs. 6.09 mm/12.90° for simulated images and reduced MSE/L1/DSSIM/Total errors of 18.07% / 19.02% / 0.04% / 29.59% for real ASL test images) and 4.4 times (ARN vs. SPM: 0.50 s vs. 2.21 s) faster speed compared to SPM. The trained ARN can be generalized to align ASL perfusion image time series acquired with different scanners, and from different image resolutions, and from healthy or diseased populations. The results demonstrated that our ARN markedly outperforms the iteration-based SPM both for simulated motion and real acquisitions in terms of registration accuracy, speed, and generalization.

Affective experience in a virtual crowd regulates perceived travel time.

Time sometimes feels like it is flying by or slowing down. Previous research indicates objective number of items, subjective affect, and heart rate all can influence the experience of time. While these factors are usually tested in isolation with simple stimuli in the laboratory, here we examined them together in the ecological context of a virtual subway ride. We hypothesized that subjective affective experience associated with objective crowding lengthens subjective trip duration. Participants (N = 41) experienced short (1-2 min) immersive virtual reality subway trips with different levels of public crowding. Consistent with the immersive nature of decreased interpersonal virtual space, increased crowding decreased pleasantness and increased the unpleasantness of a trip. Virtual crowding also lengthened perceived trip duration. The presence of one additional person per square meter of the train significantly increased perceived travel time by an average of 1.8 s. Degree of pleasant relative to unpleasant affect mediated why crowded trips felt longer. Independently of crowding and affect, heart rate changes were related to experienced trip time. These results demonstrate socioemotional regulation of the experience of time and that effects of social crowding on perception and affect can be reliably created during a solitary virtual experience. This study demonstrates a novel use of Virtual Reality technology for testing psychological theories in ecologically valid and highly controlled settings. Supplementary Information: The online version contains supplementary material available at 10.1007/s10055-022-00713-8.

Emotional Objectivity: Neural Representations of Emotions and Their Interaction with Cognition.

Recent advances in our understanding of information states in the human brain have opened a new window into the brain's representation of emotion. While emotion was once thought to constitute a separate domain from cognition, current evidence suggests that all events are filtered through the lens of whether they are good or bad for us. Focusing on new methods of decoding information states from brain activation, we review growing evidence that emotion is represented at multiple levels of our sensory systems and infuses perception, attention, learning, and memory. We provide evidence that the primary function of emotional representations is to produce unified emotion, perception, and thought (e.g., "That is a good thing") rather than discrete and isolated psychological events (e.g., "That is a thing. I feel good"). The emergent view suggests ways in which emotion operates as a fundamental feature of cognition, by design ensuring that emotional outcomes are the central object of perception, thought, and action.

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.

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.

Episodic autobiographical memory is associated with variation in the size of hippocampal subregions.

Striking individual differences exist in the human capacity to recollect past events, yet, little is known about the neural correlates of such individual differences. Studies investigating hippocampal volume in relation to individual differences in laboratory measures of episodic memory in young adults suggest that whole hippocampal volume is unrelated (or even negatively associated) with episodic memory. However, anatomical and functional specialization across hippocampal subregions suggests that individual differences in episodic memory may be linked to particular hippocampal subregions, as opposed to whole hippocampal volume. Given that the DG/CA2/3 circuitry is thought to be especially critical for supporting episodic memory in humans, we predicted that the volume of this region would be associated with individual variability in episodic memory. This prediction was supported using high-resolution MRI of the hippocampal subfields and measures of real-world (autobiographical) episodic memory. In addition to the association with DG/CA2/3 , we further observed a relationship between episodic autobiographical memory and subiculum volume, whereas no association was observed with CA1 or with whole hippocampal volume. These findings provide insight into the possible neural substrates that mediate individual differences in real-world episodic remembering in humans.

Emotional memories and how your life may depend upon them.

In this commentary, we discuss how one's internal body state and the appraisals an individual utilizes at encoding alter later episodic memory irrespective of social discourse. We suggest that the purpose of episodic memory is originally the preservation of the self, which may have been co-opted to navigating the social world.

Reading What the Mind Thinks From How the Eye Sees.

Human eyes convey a remarkable variety of complex social and emotional information. However, it is unknown which physical eye features convey mental states and how that came about. In the current experiments, we tested the hypothesis that the receiver's perception of mental states is grounded in expressive eye appearance that serves an optical function for the sender. Specifically, opposing features of eye widening versus eye narrowing that regulate sensitivity versus discrimination not only conveyed their associated basic emotions (e.g., fear vs. disgust, respectively) but also conveyed opposing clusters of complex mental states that communicate sensitivity versus discrimination (e.g., awe vs. suspicion). This sensitivity-discrimination dimension accounted for the majority of variance in perceived mental states (61.7%). Further, these eye features remained diagnostic of these complex mental states even in the context of competing information from the lower face. These results demonstrate that how humans read complex mental states may be derived from a basic optical principle of how people see.

The Face of Distaste: A Preliminary Study.

Distaste is a primitive rejection impulse triggered by the ingestion of unpleasant tasting substances, many of which are toxic. Theoretical work has suggested that distaste may be the evolutionary precursor for both physical disgust, which serves to defend against disease and other threats to biological fitness, and moral disgust, which defends against threats to the social order. Consistent with this proposal, recent work has found that the facial expression of distaste may be similar to that of disgust. Specifically, raising of the upper lip has been reported in distaste, physical disgust, and moral disgust. However, competing evidence suggests that distaste and disgust expressions may differ, and the facial expressions of adult humans in response to distasteful stimuli remain poorly specified. To address this issue, we conducted a preliminary experiment to investigate the upper lip raise in adult volunteers (N = 15) as they tasted unpleasant, pleasant, and neutral liquids. We found increased raising of the upper lip for bitter and salty tastes relative to water and sweet, suggesting that the upper lip raise is indeed part of the distaste expression. Given evidence that the upper lip raise is also present in physical and moral disgust, these results are consistent with the proposed origins of disgust in distaste.

Neurogenetic variations in norepinephrine availability enhance perceptual vividness.

Emotionally salient aspects of the world are experienced with greater perceptual vividness than mundane ones; however, such emotionally enhanced vividness (EEV) may be experienced to different degrees for different people. We examined whether BOLD activity associated with a deletion variant of the ADRA2b gene coding for the α2b adrenoceptor modulates EEV in humans. Relative to noncarriers, ADRA2b deletion carriers showed higher levels of perceptual vividness, with the ventromedial prefrontal cortex (VMPFC) showing greater modulation by EEV. Deletion carriers were also more sensitive to the featural salience of the images, suggesting a more pervasive role of norepinephrine in perceptual encoding. Path analysis revealed that, whereas a simple model by which the amygdala modulated the lateral occipital complex best characterized EEV-related activity in noncarriers, contributions of an additional VMPFC pathway best characterized deletion carriers. Thus, common norepinephrine-related neurogenetic differences enhance the subjective vividness of perceptual experience and its emotional enhancement.

What BANE can offer GANE: Individual differences in function of hotspot mechanisms.

In this commentary we focus on individual differences in proposed mechanisms underlying arousal-based enhancement of prioritized stimuli. We discuss the potential of genotyping studies for examining effects of noradrenergic processes on stimulus prioritization in humans and stress the importance of potential individual differences in the activity of specific receptor subtypes in hotspot processes proposed by the GANE model.

Representation of affect in sensory cortex.

Contemporary neuroscience suggests that perception is perhaps best understood as a dynamically iterative process that does not honor cleanly segregated "bottom-up" or "top-down" streams. We argue that there is substantial empirical support for the idea that affective influences infiltrate the earliest reaches of sensory processing and even that primitive internal affective dimensions (e.g., goodness-to-badness) are represented alongside physical dimensions of the external world.

KIBRA polymorphism is associated with individual differences in hippocampal subregions: evidence from anatomical segmentation using high-resolution MRI.

The KIBRA gene has been associated with episodic memory in several recent reports; carriers of the T-allele show enhanced episodic memory performance relative to noncarriers. Gene expression studies in human and rodent species show high levels of KIBRA in the hippocampus, particularly in the subfields. The goal of the present study was to determine whether the KIBRA C→T polymorphism is also associated with volume differences in the human hippocampus and whether specific subfields are differentially affected by KIBRA genotype. High-resolution magnetic resonance imaging (T2-weighted, voxel size=0.4×0.4 mm, in-plane) was used to manually segment hippocampal cornu ammonis (CA) subfields, dentate gyrus (DG), and the subiculum as well as adjacent medial temporal lobe cortices in healthy carriers and noncarriers of the KIBRA T-allele (rs17070145). Overall, we found that T-carriers had a larger hippocampal volume relative to noncarriers. The structural differences observed were specific to the CA fields and DG regions of the hippocampus, suggesting a potential neural mechanism for the effects of KIBRA on episodic memory performance reported previously.

Optical origins of opposing facial expression actions.

Darwin theorized that emotional expressions originated as opposing functional adaptations for the expresser, not as distinct categories of social signals. Given that two thirds of the eye's refractive power comes from the cornea, we examined whether opposing expressive behaviors that widen the eyes (e.g., fear) or narrow the eyes (e.g., disgust) may have served as an optical trade-off, enhancing either sensitivity or acuity, thereby promoting stimulus localization ("where") or stimulus discrimination ("what"), respectively. An optical model based on eye apertures of posed fear and disgust expressions supported this functional trade-off. We then tested the model using standardized optometric measures of sensitivity and acuity. We demonstrated that eye widening enhanced stimulus detection, whereas eye narrowing enhanced discrimination, each at the expense of the other. Opposing expressive actions around the eye may thus reflect origins in an optical principle, shaping visual encoding at its earliest stage-how light is cast onto the retina.

Attentional modulation of primary interoceptive and exteroceptive cortices.

How exteroceptive attention (EA) alters neural representations of the external world is well characterized, yet little is known about how interoceptive attention (IA) alters neural representations of the body's internal state. We contrasted visual EA against IA toward respiration. Visual EA modulated striate and extrastriate cortices and a lateral frontoparietal "executive" network. By contrast, respiratory IA modulated a posterior insula region sensitive to respiratory frequency, consistent with primary interoceptive cortex, and a posterior limbic and medial parietal network, including the hippocampus, precuneus, and midcingulate cortex. Further distinguishing between EA and IA networks, attention-dependent connectivity analyses revealed that EA enhanced visual cortex connectivity with the inferior parietal lobule and pulvinar of the thalamus, while IA enhanced insula connectivity with the posterior ventromedial thalamus, a relay of the laminar I spinothalamocortical pathway supporting interoceptive afference. Despite strong connectivity between the posterior and the anterior insula, anatomical parcellation of the insula revealed a gradient of IA to EA recruitment along its posterior-anterior axis. These results suggest that distinct networks may support EA and IA. Furthermore, the anterior insula is not an area of pure body awareness but may link representations of the outside world with the body's internal state--a potential basis for emotional experience.

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.

Psychophysical and neural evidence for emotion-enhanced perceptual vividness.

Highly emotional events are associated with vivid "flashbulb" memories. Here we examine whether the flashbulb metaphor characterizes a previously unknown emotion-enhanced vividness (EEV) during initial perceptual experience. Using a magnitude estimation procedure, human observers estimated the relative magnitude of visual noise overlaid on scenes. After controlling for computational metrics of objective visual salience, emotional salience was associated with decreased noise, or heightened perceptual vividness, demonstrating EEV, which predicted later memory vividness. Event-related potentials revealed a posterior P2 component at ∼200 ms that was associated with both increased emotional salience and decreased objective noise levels, consistent with EEV. Blood oxygenation level-dependent response in the lateral occipital complex (LOC), insula, and amygdala predicted online EEV. The LOC and insula represented complimentary influences on EEV, with the amygdala statistically mediating both. These findings indicate that the metaphorical vivid light surrounding emotional memories is embodied directly in perceptual cortices during initial experience, supported by cortico-limbic interactions.

Social transmission of the sensory benefits of eye widening in fear expressions.

Facial expressions may have originated from a primitive sensory regulatory function that was then co-opted and further shaped for the purposes of social utility. In the research reported here, we tested such a hypothesis by investigating the functional origins of fear expressions for both the expresser and the observer. We first found that fear-based eye widening enhanced target discrimination in the available visual periphery of the expresser by 9.4%. We then found that fear-based eye widening enhanced observers' discrimination of expressers' gaze direction and facilitated observers' responses when locating eccentric targets. We present evidence that this benefit was driven by neither the perceived emotion nor attention but, rather, by an enhanced physical signal originating from greater exposure of the iris and sclera. These results highlight the coevolution of sensory and social regulatory functions of emotional expressions by showing that eye widening serves to enhance processing of important environmental events in the visual fields of both expresser and observer.

Genes for emotion-enhanced remembering are linked to enhanced perceiving.

Emotionally enhanced memory and susceptibility to intrusive memories after trauma have been linked to a deletion variant (i.e., a form of a gene in which certain amino acids are missing) of ADRA2B, the gene encoding subtype B of the α2-adrenergic receptor, which influences norepinephrine activity. We examined in 207 participants whether variations in this gene are responsible for individual differences in affective influences on initial encoding that alter perceptual awareness. We examined the attentional blink, an attentional impairment during rapid serial visual presentation, for negatively arousing, positively arousing, and neutral target words. Overall, the attentional blink was reduced for emotional targets for ADRA2B-deletion carriers and noncarriers alike, which reveals emotional sparing (i.e., reduction of the attentional impairment for words that are emotionally significant). However, deletion carriers demonstrated a further, more pronounced emotional sparing for negative targets. This finding demonstrates a contribution of genetics to individual differences in the emotional subjectivity of perception, which in turn may be linked to biases in later memory.

It takes two to talk: a second-person neuroscience approach to language learning.

Language is a social act. We have previously argued that language remains embedded in sociality because the motivation to communicate exists only within a social context. Schilbach et al. underscore the importance of studying linguistic behavior from within the motivated, socially interactive frame in which it is learnt and used, as well as provide testable hypotheses for a participatory, second-person neuroscience approach to language learning.