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PurposeFor more than 20 years, there has been an international, multidisciplinary effort to develop retinal prostheses to restore functional vision to patients blinded by retinal degeneration. We developed a novel subretinal prosthesis with 1512 optically addressed silicon nanowire photodiodes, which transduce incident light into an electrical stimulation of the remaining retinal circuitry. This study was conducted to evaluate the efficacy of optically driving the subretinal prosthesis to produce visual cortex activation via electrical stimulation of the retina.MethodsWe measured electrically evoked potential responses (EEPs) in rabbit visual cortex in response to illumination of the subretinal nanowire prosthesis with pulsed 852-nm infrared (IR) light. We compared the EEP responses to visually evoked potential responses (VEPs) to pulsed 532-nm visible light (positive control) and pulsed 852-nm IR light (negative control).ResultsActivating the devices with IR light produced EEP responses with a significantly higher trough-to-peak amplitude (54.17 ± 33.4 μV) than IR light alone (24.07 ± 22.1 μV) or background cortical activity (23.22 ± 17.2 μV). EEP latencies were significantly faster than focal VEP latencies. Focal VEPs produced significantly higher amplitudes (94.88 ± 43.3 μV) than EEPs. We also demonstrated how an electrode placed on the cornea can be used as a noninvasive method to monitor the function of the implant.ConclusionsThese results show that subretinal electrical stimulation with nanowire electrodes can elicit EEPs in the visual cortex, providing evidence for the viability of a subretinal nanowire prosthetic approach for vision restoration.

To combat retinal degeneration, healthy fetal retinal sheets have been successfully transplanted into both rodent models and humans, with synaptic connectivity between transplant and degenerated host retina having been confirmed. In rodent studies, transplants have been shown to restore responses to flashes of light in a region of the superior colliculus corresponding to the location of the transplant in the host retina. To determine the quality and detail of visual information provided by the transplant, visual responsivity was studied here at the level of visual cortex where higher visual perception is processed. For our model, we used the transgenic Rho-S334ter line-3 rat (both sexes), which loses photoreceptors at an early age and is effectively blind at postnatal day 30. These rats received fetal retinal sheet transplants in one eye between 24 and 40 d of age. Three to 10 months following surgery, visually responsive neurons were found in regions of primary visual cortex matching the transplanted region of the retina that were as highly selective as normal rat to stimulus orientation, size, contrast, and spatial and temporal frequencies. Conversely, we found that selective response properties were largely absent in nontransplanted line-3 rats. Our data show that fetal retinal sheet transplants can result in remarkably normal visual function in visual cortex of rats with a degenerated host retina and represents a critical step toward developing an effective remedy for the visually impaired human population.SIGNIFICANCE STATEMENT Age-related macular degeneration and retinitis pigmentosa lead to profound vision loss in millions of people worldwide. Many patients lose both retinal pigment epithelium and photoreceptors. Hence, there is a great demand for the development of efficient techniques that allow for long-term vision restoration. In this study, we transplanted dissected fetal retinal sheets, which can differentiate into photoreceptors and integrate with the host retina of rats with severe retinal degeneration. Remarkably, we show that transplants generated visual responses in cortex similar in quality to normal rats. Furthermore, transplants preserved connectivity within visual cortex and the retinal relay from the lateral geniculate nucleus to visual cortex, supporting their potential application in curing vision loss associated with retinal degeneration.

The enhancement of neuronal responses in many visual areas while animals perform spatial attention tasks has widely been thought to be the neural correlate of visual attention, but it is unclear whether the presence or absence of this modulation contributes to our striking inability to notice changes in change blindness examples. We asked whether neuronal responses in visual area V4 and the lateral intraparietal area (LIP) in posterior parietal cortex could explain the limited ability of subjects to attend multiple items in a display. We trained animals to perform a change detection task in which they had to compare 2 arrays of stimuli separated briefly in time and found that each animal's performance decreased as function of set-size. Neuronal discriminability in V4 was consistent across set-sizes, but decreased for higher set-sizes in LIP. The introduction of a reward bias produced attentional enhancement in V4, but this could not explain the vast improvement in performance, whereas the enhancement in LIP responses could. We suggest that behavioral set-size effects and the marked improvement in performance with focused attention may not be related to response enhancement in V4 but, instead, may occur in or on the way to LIP.

Mounting evidence suggests that the medial temporal lobe (MTL) and striatal learning systems support different forms of learning, which can be competitive or cooperative depending on task demands. We have previously shown how activity in these regions can be modulated in a conditional visuomotor associative learning task based on the consistency of response mappings or reward feedback (Mattfeld & Stark, 2015). Here, we examined the shift in learning towards the MTL and away from the striatum by placing strong demands on pattern separation, a process of orthogonalizing similar inputs into distinct representations. Mnemonically, pattern separation processes have been shown to rely heavily on processing in the hippocampus. Therefore, we predicted modulation of hippocampal activity by pattern separation demands, but no such modulation of striatal activity. Using a variant of the conditional visuomotor associative learning task that we have used previously, we presented participants with two blocked conditions: items with high and low perceptual overlap during functional magnetic resonance imaging (fMRI). As predicted, we observed learning-related activity in the hippocampus, which was greater in the high than the low overlap condition, particularly in the dentate gyrus. In contrast, the associative striatum also showed learning related activity, but it was not modulated by overlap condition. Using functional connectivity analyses, we showed that the correlation between the hippocampus and dentate gyrus with the associative striatum was differentially modulated by high vs. low overlap, suggesting that the coordination between these regions was affected when pattern separation demands were high. These findings contribute to a growing literature that suggests that the hippocampus and striatal network both contribute to the learning of arbitrary associations that are computationally distinct and can be altered by task demands.

Retinal waves are bursts of correlated activity that occur prior to eye opening and provide a critical source of activity that drives the refinement of retinofugal projections. Retinal waves are thought to be initiated spontaneously with their spatiotemporal features dictated by immature neural circuits. Here we demonstrate that, during the second postnatal week in mice, changes in light intensity dictate where and when a subset of retinal waves are triggered via activation of conventional photoreceptors. Propagation properties of triggered waves are indistinguishable from spontaneous waves, indicating that they are activating the same retinal circuits. Using whole-brain imaging techniques, we demonstrate that light deprivation prior to eye opening diminishes eye-specific segregation of the retinal projections to the dorsolateral geniculate nucleus of the thalamus, but not other retinal targets. These data indicate that light that passes through the closed eyelids plays a critical role in the development of the image-forming visual system.

BackgroundProper patterning of dendritic and axonal arbors is a critical step in the formation of functional neuronal circuits. Developing circuits rely on an array of molecular cues to shape arbor morphology, but the underlying mechanisms guiding the structural formation and interconnectivity of pre- and postsynaptic arbors in real time remain unclear. Here we explore how Down syndrome cell adhesion molecule (DSCAM) differentially shapes the dendritic morphology of central neurons and their presynaptic retinal ganglion cell (RGC) axons in the developing vertebrate visual system.MethodsThe cell-autonomous role of DSCAM, in tectal neurons and in RGCs, was examined using targeted single-cell knockdown and overexpression approaches in developing Xenopus laevis tadpoles. Axonal arbors of RGCs and dendritic arbors of tectal neurons were visualized using real-time in vivo confocal microscopy imaging over the course of 3 days.ResultsIn the Xenopus visual system, DSCAM immunoreactivity is present in RGCs, cells in the optic tectum and the tectal neuropil at the time retinotectal synaptic connections are made. Downregulating DSCAM in tectal neurons significantly increased dendritic growth and branching rates while inducing dendrites to take on tortuous paths. Overexpression of DSCAM, in contrast, reduced dendritic branching and growth rate. Functional deficits mediated by tectal DSCAM knockdown were examined using visually guided behavioral assays in swimming tadpoles, revealing irregular behavioral responses to visual stimulus. Functional deficits in visual behavior also corresponded with changes in VGLUT/VGAT expression, markers of excitatory and inhibitory transmission, in the tectum. Conversely, single-cell DSCAM knockdown in the retina revealed that RGC axon arborization at the target is influenced by DSCAM, where axons grew at a slower rate and remained relatively simple. In the retina, dendritic arbors of RGCs were not affected by the reduction of DSCAM expression.ConclusionsTogether, our observations implicate DSCAM in the control of both pre- and postsynaptic structural and functional connectivity in the developing retinotectal circuit, where it primarily acts as a neuronal brake to limit and guide postsynaptic dendrite growth of tectal neurons while it also facilitates arborization of presynaptic RGC axons cell autonomously.

A growing body of evidence suggests that children succeed in nontraditional false-belief tasks in the first years of life. However, few studies have examined individual differences in infants' and toddlers' performance on these tasks. Here we investigated whether parental use of mental-state language (i.e. think, understand), which predicts children's performance on elicited-response false-belief tasks at older ages, also predicts toddlers' performance on a nontraditional task. We tested 2.5-year-old children in a verbal nontraditional false-belief task that included two looking time measures, anticipatory looking and preferential looking, and measured parents' use of mental-state language during a picture-book task. Parents' use of mental-state language positively predicted children's performance on the anticipatory-looking measure of the nontraditional task. These results provide the first evidence that social factors relate to children's false-belief understanding prior to age 3 and that this association extends to performance on nontraditional tasks. These findings add to a growing number of studies suggesting that mental-state language supports mental-state understanding across the lifespan.

Assessments of the mouse visual system based on spatial-frequency analysis imply that its visual capacity is low, with few neurons responding to spatial frequencies greater than 0.5 cycles per degree. However, visually mediated behaviors, such as prey capture, suggest that the mouse visual system is more precise. We introduce a stimulus class-visual flow patterns-that is more like what the mouse would encounter in the natural world than are sine-wave gratings but is more tractable for analysis than are natural images. We used 128-site silicon microelectrodes to measure the simultaneous responses of single neurons in the primary visual cortex (V1) of alert mice. While holding temporal-frequency content fixed, we explored a class of drifting patterns of black or white dots that have energy only at higher spatial frequencies. These flow stimuli evoke strong visually mediated responses well beyond those predicted by spatial-frequency analysis. Flow responses predominate in higher spatial-frequency ranges (0.15-1.6 cycles per degree), many are orientation or direction selective, and flow responses of many neurons depend strongly on sign of contrast. Many cells exhibit distributed responses across our stimulus ensemble. Together, these results challenge conventional linear approaches to visual processing and expand our understanding of the mouse's visual capacity to behaviorally relevant ranges.

Decision-making becomes slower when more choices are available. Existing models attribute this slowing to poor sensory processing, to attenuated rates of sensory evidence accumulation, or to increases in the amount of evidence required before committing to a decision (a higher decision threshold). However, studies have not isolated the effects of having more choices on sensory and decision-related processes from changes in task difficulty and divided attention. Here, we controlled task difficulty while independently manipulating the distribution of attention and the number of choices available to male and female human observers. We used EEG to measure steady-state visually evoked potentials (SSVEPs) and a frontal late positive deflection (LPD), EEG markers of sensory and postsensory decision-related processes, respectively. We found that dividing attention decreased SSVEP and LPD amplitudes, consistent with dampened sensory responses and slower rates of evidence accumulation, respectively. In contrast, having more choices did not alter SSVEP amplitude and led to a larger LPD. These results suggest that having more options largely spares early sensory processing and slows down decision-making via a selective increase in decision thresholds.SIGNIFICANCE STATEMENT When more choices are available, decision-making becomes slower. We tested whether this phenomenon is due to poor sensory processing, to reduced rates of evidence accumulation, or to increases in the amount of evidence required before committing to a decision (a higher decision threshold). We measured choice modulations of sensory and decision-related neural responses using EEG. We also minimized potential confounds from changes in the distribution of attention and task difficulty, which often covary with having more choices. Dividing attention reduced the activity levels of both sensory and decision-related responses. However, having more choices did not change sensory processing and led to larger decision-related responses. These results suggest that having more choices spares sensory processing and selectively increases decision thresholds.

Tobacco smoking is the most common preventable cause of death in the US. Nicotine is considered the primary constituent responsible for tobacco addiction. Its paradoxically high abuse potential may reflect behavioral control by drug-associated stimuli, which appears to play a larger role for tobacco dependence than for other abused drugs. We tested a potential explanation, hypothesizing that nicotine enhances associative learning, the mechanism underlying the conditioning of drug-associated stimuli. Thirty-two non-smokers were exposed to transdermal nicotine (7 mg/24 h) and placebo in a double-blind cross-over study and tested with behavioral paradigms designed to isolate incidental stimulus-stimulus or stimulus-response learning. The stop signal task required speeded gender judgments of face stimuli. A tone signaled when to withhold the response. Unbeknownst to participants, some faces were always paired with stop trials. Nicotine enhanced the facilitation of stop-responses to these stimuli, and the slowing of go-responses when previously stop-associated stimuli were paired with go trials, indicating stronger associations between paired stimuli and the stop signal/stop response. Another task required feedback-based learning of associations between pairs of shape stimuli. Five pairs were made from either ten different stimuli, or from different combinations of two identical sets of five stimuli with correct associations depending on contextual information. Nicotine increased incorrect choices of stimuli that were associated in a different context, indicating stronger stimulus-stimulus associations at the expense of flexible context-adaptive behavior. The results indicate that nicotine can enhance incidental associative learning, a mechanism that may promote the formation of smoking-associated stimuli and cue-controlled drug-taking.

Hoarding disorder (HD) has been hypothesized to arise from deficits in error monitoring and abnormalities in emotional processing, but the relationship between error monitoring and emotional processing has not been examined. We examined measures of self-report, as well as behavioral, physiological, and facial responses to errors during a Stop-Change Task. 25 participants with HD and 32 healthy controls (HC) were recruited. Participants reported on number of errors committed and pre/post emotional response to errors. Skin conductance response (SCR) during correct and error commission trials was examined. Facial expression during task performance was coded for self-conscious and negative emotions. HD and HC participants had significantly different error rates but comparable error correction and post-error slowing. SCR was significantly lower for HD during error commission than for HC. During error trials, HD participants showed a significant deficit in displays of self-conscious emotions compared to HC. Self-reported emotions were increased in HD, with more negative and self-conscious emotion reported than was reported for HC participants. These findings suggest that hypoactive emotional responding at a physiological level may play a role in how errors are processed in individuals with HD.

The optic tectum (TeO), or superior colliculus, is a multisensory midbrain center that organizes spatially orienting responses to relevant stimuli. To define the stimulus with the highest priority at each moment, a network of reciprocal connections between the TeO and the isthmi promotes competition between concurrent tectal inputs. In the avian midbrain, the neurons mediating enhancement and suppression of tectal inputs are located in separate isthmic nuclei, facilitating the analysis of the neural processes that mediate competition. A specific subset of radial neurons in the intermediate tectal layers relay retinal inputs to the isthmi, but at present it is unclear whether separate neurons innervate individual nuclei or a single neural type sends a common input to several of them. In this study, we used in vitro neural tracing and cell-filling experiments in chickens to show that single neurons innervate, via axon collaterals, the three nuclei that comprise the isthmotectal network. This demonstrates that the input signals representing the strength of the incoming stimuli are simultaneously relayed to the mechanisms promoting both enhancement and suppression of the input signals. By performing in vivo recordings in anesthetized chicks, we also show that this common input generates synchrony between both antagonistic mechanisms, demonstrating that activity enhancement and suppression are closely coordinated. From a computational point of view, these results suggest that these tectal neurons constitute integrative nodes that combine inputs from different sources to drive in parallel several concurrent neural processes, each performing complementary functions within the network through different firing patterns and connectivity.

Individuals can quickly and effortlessly recognize facial expressions, which is critical for social perception and emotion regulation. This sensitivity to even slight facial changes could result in unstable percepts of an individual's expression over time. The visual system must therefore balance accuracy with maintaining perceptual stability. However, previous research has focused on our sensitivity to changing expressions, and the mechanism behind expression stability remains an open question. Recent results demonstrate that perception of facial identity is systematically biased toward recently seen visual input. This positive perceptual pull, or serial dependence, may help stabilize perceived expression. To test this, observers judged random facial expression morphs ranging from happy to sad to angry. We found a pull in perceived expression toward previously seen expressions, but only when the 1-back and current face had similar identities. Our results are consistent with the existence of the continuity field for expression, a specialized mechanism that promotes the stability of emotion perception, which could help facilitate social interactions and emotion regulation.

OBJECTIVE:The convergence of optogenetic and large-scale neural recording technologies opens enormous opportunities for studying brain function. However, compared to the widespread use of optogenetics or recordings as standalone methods, the joint use of these techniques in behaving animals is much less well developed. A simple but poorly scalable solution has been to implant conventional optical fibers together with extracellular microelectrodes. A more promising approach has been to combine microfabricated light emission sources with multielectrode arrays. However, a challenge remains in how to compactly and scalably integrate optical output and electronic readout structures on the same device. Here we took a step toward addressing this issue by using nanofabrication techniques to develop a novel implantable optoelectronic probe. APPROACH:This device contains multiple photonic grating couplers connected with waveguides for out-of-plane light emission, monolithically integrated with a microlectrode array on the same silicon substrate. To demonstrate the device's operation in vivo, we record cortical activity from awake head-restrained mice. MAIN RESULTS:We first characterize photo-stimulation effects on electrophysiological signals. We then assess the probe's ability to both optogenetically stimulate and electrically record neural firing. SIGNIFICANCE:This device relies on nanofabrication techniques to integrate optical stimulation and electrical readout functions on the same structure. Due to the device miniaturization capabilities inherent to nanofabrication, this optoelectronic probe technology can be further scaled to increase the throughput of manipulating and recording neural dynamics.

Classic models of attention suggest that sustained neural firing constitutes a neural correlate of sustained attention. However, recent evidence indicates that behavioral performance fluctuates over time, exhibiting temporal dynamics that closely resemble the spectral features of ongoing, oscillatory brain activity. Therefore, it has been proposed that periodic neuronal excitability fluctuations might shape attentional allocation and overt behavior. However, empirical evidence to support this notion is sparse. Here, we address this issue by examining data from large-scale subdural recordings, using two different attention tasks that track perceptual ability at high temporal resolution. Our results reveal that perceptual outcome varies as a function of the theta phase even in states of sustained spatial attention. These effects were robust at the single-subject level, suggesting that rhythmic perceptual sampling is an inherent property of the frontoparietal attention network. Collectively, these findings support the notion that the functional architecture of top-down attention is intrinsically rhythmic.

The posterior parietal cortex (PPC) has been implicated in perceptual decisions, but whether its role is specific to sensory processing or sensorimotor transformation is not well understood. Here, we trained mice to perform a go/no-go visual discrimination task and imaged the activity of neurons in primary visual cortex (V1) and PPC during engaged behavior and passive viewing. Unlike V1 neurons, which respond robustly to stimuli in both conditions, most PPC neurons respond exclusively during task engagement. To test whether signals in PPC primarily encoded the stimulus or the animal's impending choice, we image the same neurons before and after re-training mice with a reversed sensorimotor contingency. Unlike V1 neurons, most PPC neurons reflect the animal's choice of the new target stimulus after re-training. Mouse PPC is therefore strongly task-dependent, reflects choice more than stimulus, and may play a role in the transformation of visual inputs into motor commands.

Prediction of upcoming words during reading has been suggested to enhance the efficiency of discourse processing. Emerging models have postulated that predictive mechanisms require synchronous firing of neural networks, but to date, this relationship has been investigated primarily through oscillatory activity in narrow frequency bands. A recently-developed measure proposed to reflect broadband neural activity - and thereby synchronous neuronal firing - is 1/f neural noise extracted from EEG spectral power. Previous research has indicated that this measure of 1/f neural noise changes across the lifespan, and these neural changes predict age-related behavioral impairments in visual working memory. Using a cross-sectional sample of young and older adults, we examined age-related changes in 1/f neural noise and whether this measure predicted ERP correlates of successful lexical prediction during discourse comprehension. 1/f neural noise across two different language tasks revealed high within-subject correlations, indicating that this measure can provide a reliable index of individualized patterns of neural activation. In addition to age, 1/f noise was a significant predictor of N400 effects of successful lexical prediction; however, noise did not mediate age-related declines in other ERP effects. We discuss broader implications of these findings for theories of predictive processing, as well as potential applications of 1/f noise across research populations.

The current study explored the intellectual factors in false memories of 139 patients with schizophrenia, using a recognition task and an IQ test. The full-scale IQ score of the participants ranged from 57 to 144 (M = 100, SD = 14). The full IQ score had a negative correlation with false recognition in patients with schizophrenia, and positive correlations with high-confidence true recognition and discrimination rates. Further analyses with the subtests' scores revealed that false recognition was negatively correlated with scores of performance IQ (and one of its subtests: picture arrangement), whereas true recognition was positively correlated with scores of verbal IQ (and two of its subtests: information and digit span). High-IQ patients had less false recognition (overall or high-confidence false recognition), more high-confidence true recognition, and higher discrimination abilities than those with low IQ. These findings contribute to a better understanding of the cognitive mechanism in false memory of patients with schizophrenia, and are of practical relevance to the evaluation of memory reliability in patients with different intellectual levels.

Two factors play important roles in shaping perception: the allocation of selective attention to behaviorally relevant sensory features, and prior expectations about regularities in the environment. Signal detection theory proposes distinct roles of attention and expectation on decision-making such that attention modulates early sensory processing, whereas expectation influences the selection and execution of motor responses. Challenging this classic framework, recent studies suggest that expectations about sensory regularities enhance the encoding and accumulation of sensory evidence during decision-making. However, it is possible, that these findings reflect well documented attentional modulations in visual cortex. Here, we tested this framework in a group of male and female human participants by examining how expectations about stimulus features (orientation and color) and expectations about motor responses impacted electroencephalography (EEG) markers of early sensory processing and the accumulation of sensory evidence during decision-making (the early visual negative potential and the centro-parietal positive potential, respectively). We first demonstrate that these markers are sensitive to changes in the amount of sensory evidence in the display. Then we show, counter to recent findings, that neither marker is modulated by either feature or motor expectations, despite a robust effect of expectations on behavior. Instead, violating expectations about likely sensory features and motor responses impacts posterior alpha and frontal theta oscillations, signals thought to index overall processing time and cognitive conflict. These findings are inconsistent with recent theoretical accounts and suggest instead that expectations primarily influence decisions by modulating post-perceptual stages of information processing.SIGNIFICANCE STATEMENT Expectations about likely features or motor responses play an important role in shaping behavior. Classic theoretical frameworks posit that expectations modulate decision-making by biasing late stages of decision-making including the selection and execution of motor responses. In contrast, recent accounts suggest that expectations also modulate decisions by improving the quality of early sensory processing. However, these effects could instead reflect the influence of selective attention. Here we examine the effect of expectations about sensory features and motor responses on a set of electroencephalography (EEG) markers that index early sensory processing and later post-perceptual processing. Counter to recent empirical results, expectations have little effect on early sensory processing but instead modulate EEG markers of time-on-task and cognitive conflict.

Visual working memory (VWM) recruits a broad network of brain regions, including prefrontal, parietal, and visual cortices. Recent evidence supports a "sensory recruitment" model of VWM, whereby precise visual details are maintained in the same stimulus-selective regions responsible for perception. A key question in evaluating the sensory recruitment model is how VWM representations persist through distracting visual input, given that the early visual areas that putatively represent VWM content are susceptible to interference from visual stimulation.To address this question, we used a functional magnetic resonance imaging inverted encoding model approach to quantitatively assess the effect of distractors on VWM representations in early visual cortex and the intraparietal sulcus (IPS), another region previously implicated in the storage of VWM information. This approach allowed us to reconstruct VWM representations for orientation, both before and after visual interference, and to examine whether oriented distractors systematically biased these representations. In our human participants (both male and female), we found that orientation information was maintained simultaneously in early visual areas and IPS in anticipation of possible distraction, and these representations persisted in the absence of distraction. Importantly, early visual representations were susceptible to interference; VWM orientations reconstructed from visual cortex were significantly biased toward distractors, corresponding to a small attractive bias in behavior. In contrast, IPS representations did not show such a bias. These results provide quantitative insight into the effect of interference on VWM representations, and they suggest a dynamic tradeoff between visual and parietal regions that allows flexible adaptation to task demands in service of VWM.SIGNIFICANCE STATEMENT Despite considerable evidence that stimulus-selective visual regions maintain precise visual information in working memory, it remains unclear how these representations persist through subsequent input. Here, we used quantitative model-based fMRI analyses to reconstruct the contents of working memory and examine the effects of distracting input. Although representations in the early visual areas were systematically biased by distractors, those in the intraparietal sulcus appeared distractor-resistant. In contrast, early visual representations were most reliable in the absence of distraction. These results demonstrate the dynamic, adaptive nature of visual working memory processes, and provide quantitative insight into the ways in which representations can be affected by interference. Further, they suggest that current models of working memory should be revised to incorporate this flexibility.

While much of memory research takes an observer-centric focus looking at participant performance, recent work has pinpointed important item-centric effects on memory, or how intrinsically memorable a given stimulus is. However, little is known about the neural correlates of memorability during memory retrieval, or how such correlates relate to subjective memory behavior. Here, stimuli and blood-oxygen-level dependent data from a prior functional magnetic resonance imaging (fMRI) study were reanalyzed using a memorability-based framework. In that study, sixteen participants studied 200 novel face images and were scanned while making recognition memory judgments on those faces, interspersed with 200 unstudied faces. In the current investigation, memorability scores for those stimuli were obtained through an online crowd-sourced (N = 740) continuous recognition test that measured each image's corrected recognition rate. Representational similarity analyses were conducted across the brain to identify regions wherein neural pattern similarity tracked item-specific effects (stimulus memorability) versus observer-specific effects (individual memory performance). We find two non-overlapping sets of regions, with memorability-related information predominantly represented within ventral and medial temporal regions and memory retrieval outcome-related information within fronto-parietal regions. These memorability-based effects persist regardless of image history, implying that coding of stimulus memorability may be a continuous and automatic perceptual process.

Cigarette craving contributes substantially to the maintenance of tobacco use disorder. Behavioral strategies to regulate craving may facilitate smoking cessation but remain underexplored. We adapted an emotion-regulation strategy, using proximal/distal self-positioning, to the context of cigarette craving to examine craving regulation in 42, daily smokers (18-25 years old). After overnight abstinence from smoking, before and after smoking their first cigarette of the day, participants viewed videos of natural scenes presenting young adults who were either smoking cigarettes ("smoke") or not ("non-smoke"). Before each video, participants were instructed to imagine themselves either immersed in the scene ("close") or distanced from it ("far"). They rated their craving after each video. Task-based fMRI data are presented for a subsample of participants (N = 21). We found main effects of smoking, instruction, and video type on craving-lower ratings after smoking than before, following the "far" vs. "close" instructions, and when viewing non-smoke vs. smoke videos. Before smoking, "smoke" vs. "non-smoke" videos elicited activation in, orbitofrontal cortex, anterior cingulate, lateral parietal cortex, mid-occipital cortex, ventral striatum, dorsal caudate, and midbrain. Smoking reduced activation in anterior cingulate, left inferior frontal gyrus, and bilateral temporal poles. Activation was reduced in the ventral striatum and medial prefrontal cortex after the "far" vs. the "close" instruction, suggesting less engagement with the stimuli during distancing. The results indicate that proximal/distal regulation strategies impact cue-elicited craving, potentially via downregulation of the ventral striatum and medial prefrontal cortex, and that smoking during abstinence may increase cognitive control capacity during craving regulation.

Individuals with autism and intellectual impairments tend to be excluded from research due to their difficulties with methodological compliance. This study focuses on using Teaching with Acoustic Guidance-TAGteach-to behaviorally prepare children with autism and a IQ ≤ 80 to participate in a study on neurofeedback training (NFT). Seven children (ages 6-8) learned the prerequisite skills identified in a task analysis in an average of 5 h of TAGteach training, indicating that this is a feasible method of preparing intellectually-impaired children with autism to participate in NFT and task-dependent electroencephalography measures. TAGteach may thus have the potential to augment this population's ability to participate in less accessible treatments and behavioral neuroscientific studies.

Cleaner shrimp and their reef fish clients are an interspecific mutualistic interaction that is thought to be mediated by signals, and a useful system for studying the dynamics of interspecific signalling. To demonstrate signalling, one must show that purported signals at minimum (a) result in a consistent state change in the receiver and (b) contain reliable information about the sender's intrinsic state or future behaviour. Additionally, signals must be perceptible by receivers. Here, we document fundamental attributes of the signalling system between the cleaner shrimp Ancylomenes pedersoni and its clients. First, we use sequential analysis of in situ behavioural interactions to show that cleaner antenna whipping reliably predicts subsequent cleaning. If shrimp do not signal via antenna whipping, clients triple their likelihood of being cleaned by adopting darker coloration over a matter of seconds, consistent with dark colour change signalling that clients want cleaning. Using experimental manipulations, we found that visual stimuli are sufficient to elicit antenna whipping, and that shrimp are more likely to 'clean' dark than light visual stimuli. Lastly, we show that antenna whipping and colour change are perceptible when accounting for the intended receiver's visual acuity and spectral sensitivity, which differ markedly between cleaners and clients. Our results show that signalling by both cleaners and clients can initiate and mediate their mutualistic interaction.

Visual motion is an ethologically important stimulus throughout the animal kingdom. In primates, motion perception relies on specific higher-order cortical regions. Although mouse primary visual cortex (V1) and higher-order visual areas show direction-selective (DS) responses, their role in motion perception remains unknown. Here, we tested whether V1 is involved in motion perception in mice. We developed a head-fixed discrimination task in which mice must report their perceived direction of motion from random dot kinematograms (RDKs). After training, mice made around 90% correct choices for stimuli with high coherence and performed significantly above chance for 16% coherent RDKs. Accuracy increased with both stimulus duration and visual field coverage of the stimulus, suggesting that mice in this task integrate motion information in time and space. Retinal recordings showed that thalamically projecting On-Off DS ganglion cells display DS responses when stimulated with RDKs. Two-photon calcium imaging revealed that neurons in layer (L) 2/3 of V1 display strong DS tuning in response to this stimulus. Thus, RDKs engage motion-sensitive retinal circuits as well as downstream visual cortical areas. Contralateral V1 activity played a key role in this motion direction discrimination task because its reversible inactivation with muscimol led to a significant reduction in performance. Neurometric-psychometric comparisons showed that an ideal observer could solve the task with the information encoded in DS L2/3 neurons. Motion discrimination of RDKs presents a powerful behavioral tool for dissecting the role of retino-forebrain circuits in motion processing.

Understanding brain function requires technologies that can control the activity of large populations of neurons with high fidelity in space and time. We developed a multiphoton holographic approach to activate or suppress the activity of ensembles of cortical neurons with cellular resolution and sub-millisecond precision. Since existing opsins were inadequate, we engineered new soma-targeted (ST) optogenetic tools, ST-ChroME and IRES-ST-eGtACR1, optimized for multiphoton activation and suppression. Employing a three-dimensional all-optical read-write interface, we demonstrate the ability to simultaneously photostimulate up to 50 neurons distributed in three dimensions in a 550 × 550 × 100-µm3 volume of brain tissue. This approach allows the synthesis and editing of complex neural activity patterns needed to gain insight into the principles of neural codes.

Uncanny valley refers to humans' negative reaction to almost-but-not-quite-human agents. Theoretical work proposes prediction violation as an explanation for uncanny valley but no empirical work has directly tested it. Here, we provide evidence that supports this theory using event-related brain potential recordings from the human scalp. Human subjects were presented images and videos of three agents as EEG was recorded: a real human, a mechanical robot, and a realistic robot in between. The real human and the mechanical robot had congruent appearance and motion whereas the realistic robot had incongruent appearance and motion. We hypothesize that the appearance of the agent would provide a context to predict her movement, and accordingly the perception of the realistic robot would elicit an N400 effect indicating the violation of predictions, whereas the human and the mechanical robot would not. Our data confirmed this hypothesis suggesting that uncanny valley could be explained by violation of one's predictions about human norms when encountered with realistic but artificial human forms. Importantly, our results implicate that the mechanisms underlying perception of other individuals in our environment are predictive in nature.

Noninvasive stimulation of cells is crucial for the accurate examination and control of their function both at the cellular and the system levels. To address this need, we present a pioneering optical stimulation platform that does not require genetic modification of cells but instead capitalizes on unique optoelectronic properties of graphene, including its ability to efficiently convert light into electricity. We report the first studies of optical stimulation of cardiomyocytes via graphene-based biointerfaces (G-biointerfaces) in substrate-based and dispersible configurations. The efficiency of stimulation via G-biointerfaces is independent of light wavelength but can be tuned by changing the light intensity. We demonstrate that an all-optical evaluation of use-dependent drug effects in vitro can be enabled using substrate-based G-biointerfaces. Furthermore, using dispersible G-biointerfaces in vivo, we perform optical modulation of the heart activity in zebrafish embryos. Our discovery is expected to empower numerous fundamental and translational biomedical studies.

A vast number of different neuronal activity patterns could each induce a different set of activity-regulated genes. Mapping this coupling between activity pattern and gene induction would allow inference of a neuron's activity-pattern history from its gene expression and improve our understanding of activity-pattern-dependent synaptic plasticity. In genome-scale experiments comparing brief and sustained activity patterns, we reveal that activity-duration history can be inferred from gene expression profiles. Brief activity selectively induces a small subset of the activity-regulated gene program that corresponds to the first of three temporal waves of genes induced by sustained activity. Induction of these first-wave genes is mechanistically distinct from that of the later waves because it requires MAPK/ERK signaling but does not require de novo translation. Thus, the same mechanisms that establish the multi-wave temporal structure of gene induction also enable different gene sets to be induced by different activity durations.

Analogical reasoning is considered a key driver of cognitive development and is a strong predictor of academic achievement. However, it is difficult for young children, who are prone to focusing on perceptual and semantic similarities among items rather than relational commonalities. For example, in a classic A:B::C:? propositional analogy task, children must inhibit attention towards items that are visually or semantically similar to C, and instead focus on finding a relational match to the A:B pair. Competing theories of reasoning development attribute improvements in children's performance to gains in either executive functioning or semantic knowledge. Here, we sought to identify key drivers of the development of analogical reasoning ability by using eye gaze patterns to infer problem-solving strategies used by six-year-old children and adults. Children had a greater tendency than adults to focus on the immediate task goal and constrain their search based on the C item. However, large individual differences existed within children, and more successful reasoners were able to maintain the broader goal in mind and constrain their search by initially focusing on the A:B pair before turning to C and the response choices. When children adopted this strategy, their attention was drawn more readily to the correct response option. Individual differences in children's reasoning ability were also related to rule-guided behavior but not to semantic knowledge. These findings suggest that both developmental improvements and individual differences in performance are driven by the use of more efficient reasoning strategies regarding which information is prioritized from the start, rather than the ability to disengage from attractive lure items.

BackgroundFragile X premutation carriers are at increased risk for fragile X-associated tremor ataxia syndrome (FXTAS), but to date we know little about prediction of onset and rate of progression and even less about treatment of this neurodegenerative disease. Thus, the longitudinal study of carriers, and the identification of potential biomarkers and prodromal states, is essential. Here we present results of baseline assessments from an ongoing longitudinal project.MethodsThe cohort consisted of 73 men, 48 with the fragile X mental retardation 1 (FMR1) premutation (55-200 cytosine-cytosine-guanine or CGG repeats) and 25 well-matched controls (< 40 repeats) aged between 40 and 75 years. At enrollment, none met criteria for FXTAS or had any clinically significant tremor or ataxia by blinded neurological examination. The battery consisted of measures of visual memory, spatial working memory, response inhibition, motor speed and control, planning and problem solving, sustained attention, and a standardized movement disorder evaluation.ResultsContrary to expectations, there were no significant differences between premutation carriers and controls on any measure of executive function. However, the premutation carriers had significantly longer manual movement and reaction times than controls, and the significant interaction between CGG repeat and age revealed the slowest movement times among older carriers with higher CGG repeat alleles. A subset of premutation carriers had marginally lower scores on the ataxia evaluation, and they performed no differently from controls on the parkinsonism assessment.ConclusionEarly-developing cerebellar or fronto-motor tract white matter changes, previously documented in MRI studies, may underlie motor slowing that occurs before clinically observable neurological symptoms associated with FXTAS. © 2018 International Parkinson and Movement Disorder Society.

ObjectiveSeveral cross-sectional studies have reported an association between visual contrast sensitivity (a functional measure of low contrast vision) and poor cognitive performance or dementia, but no studies have investigated this association prospectively in a population-based cohort with final adjudication of mild cognitive impairment (MCI)/dementia.MethodsIn a prospective, community-based study of aging women (Study of Osteoporotic Fractures), we analyzed whether visual contrast sensitivity was associated with increased risk of MCI or dementia and/or worse performance on various cognitive tests assessed 10 years later. Contrast sensitivity was assessed at baseline in each eye using a VISTECH VCTS 6500 wall chart. MCI/dementia was adjudicated by an expert panel. Multivariate logistic and linear regression models were analyzed.ResultsOf 1,352 white (88.2%) and African American (11.8%) women with a mean age of 77.7 years (standard deviation = 3.3), 536 (39.6%) went on to develop MCI/dementia over 10 years. MCI/dementia risk was more than doubled (odds ratio = 2.16, 95% confidence interval = 1.58-2.96) in women with the lowest quartile of contrast sensitivity compared to the highest (p

The cerebral cortex is a major hub for the convergence and integration of signals from across the sensory modalities; sensory cortices, including primary regions, are no exception. Here we show that visual stimuli influence neural firing in the auditory cortex of awake male and female mice, using multisite probes to sample single units across multiple cortical layers. We demonstrate that visual stimuli influence firing in both primary and secondary auditory cortex. We then determine the laminar location of recording sites through electrode track tracing with fluorescent dye and optogenetic identification using layer-specific markers. Spiking responses to visual stimulation occur deep in auditory cortex and are particularly prominent in layer 6. Visual modulation of firing rate occurs more frequently at areas with secondary-like auditory responses than those with primary-like responses. Auditory cortical responses to drifting visual gratings are not orientation-tuned, unlike visual cortex responses. The deepest cortical layers thus appear to be an important locus for cross-modal integration in auditory cortex.SIGNIFICANCE STATEMENT The deepest layers of the auditory cortex are often considered its most enigmatic, possessing a wide range of cell morphologies and atypical sensory responses. Here we show that, in mouse auditory cortex, these layers represent a locus of cross-modal convergence, containing many units responsive to visual stimuli. Our results suggest that this visual signal conveys the presence and timing of a stimulus rather than specifics about that stimulus, such as its orientation. These results shed light on both how and what types of cross-modal information is integrated at the earliest stages of sensory cortical processing.

Behavioral tasks involving auditory cues activate inhibitory neurons within auditory cortex, leading to a reduction in the amplitude of auditory evoked response potentials (ERPs). One hypothesis is that this process, termed "task engagement," may enable context-dependent behaviors. Here we set out to determine (1) whether the medial prefrontal cortex (mPFC) plays a role in task engagement and (2) how task engagement relates to the context-dependent processing of auditory cues in male and female mice performing a decision-making task that can be guided by either auditory or visual cues. We found that, in addition to auditory ERP suppression, task engagement is associated with increased mPFC activity and an increase in theta band (4-7 Hz) synchronization between the mPFC and auditory cortex. Optogenetically inhibiting the mPFC eliminates the task engagement-induced auditory ERP suppression, while also preventing mice from switching between auditory and visual cue-based rules. However, mPFC inhibition, which eliminates task engagement-induced auditory ERP suppression, did not prevent mice from making decisions based on auditory cues. Furthermore, a more specific manipulation, selective disruption of mPFC outputs to the mediodorsal (MD) thalamus, is sufficient to prevent switching between auditory and visual rules but does not affect auditory ERPs. Based on these findings, we conclude that (1) the mPFC contributes to both task engagement and behavioral flexibility; (2) mPFC-MD projections are important for behavioral flexibility but not task engagement; and (3) task engagement, evidenced by the suppression of cortical responses to sensory input, is not required for sensory cue-guided decision making.SIGNIFICANCE STATEMENT When rodents perform choice-selection tasks based on sensory cues, neural responses to these cues are modulated compared with task-free conditions. Here we demonstrate that this phenomenon depends on the prefrontal cortex and thus represents a form of "top-down" regulation. However, we also show that this phenomenon is not critical for task performance, as rodents can make decisions based on specific sensory cues even when the task-dependent modulation of responses to those cues is abolished. Furthermore, disrupting one specific set of prefrontal outputs impairs rule switching but not the task-dependent modulation of sensory responses. These results show that the prefrontal cortex comprises multiple circuits that mediate dissociable functions related to behavioral flexibility and sensory processing.

A brain-imaging paper by Kastner and colleagues in 1999 was the first to demonstrate that merely focusing attention at a spatial location changed the baseline activity level in various regions of human visual cortex even before any stimuli appeared. The study provided a touchstone for investigating cognitive-sensory interactions and understanding the proactive endogenous signals that shape perception.

Incoming sensory signals are often ambiguous and consistent with multiple perceptual interpretations. Information from one sensory modality can help to resolve ambiguity in another modality, but the mechanisms by which multisensory associations come to influence the contents of conscious perception are unclear. We asked whether and how novel statistical information about the coupling between sounds and images influences the early stages of awareness of visual stimuli. We exposed subjects to consistent, arbitrary pairings of sounds and images and then measured the impact of this recent passive statistical learning on subjects' initial conscious perception of a stimulus by employing binocular rivalry, a phenomenon in which incompatible images presented separately to the two eyes result in a perceptual alternation between the two images. On each trial of the rivalry test, subjects were presented with a pair of rivalrous images (one of which had been consistently paired with a specific sound during exposure while the other had not) and an accompanying sound. We found that, at the onset of binocular rivalry, an image was significantly more likely to be perceived, and was perceived for a longer duration, when it was presented with its paired sound than when presented with other sounds. Our results indicate that recently acquired multisensory information helps resolve sensory ambiguity, and they demonstrate that statistical learning is a fast, flexible mechanism that facilitates this process.

Individuals with drug use disorders seek drugs over other rewarding activities, and exhibit neurochemical deficits related to dopamine, which is involved in value-based learning and decision-making. Thus, a dopaminergic disturbance may underpin drug-biased choice in addiction. Classical drug-choice assessments, which offer drug-consumption opportunities, are inappropriate for addicted individuals seeking treatment or abstaining. Fifteen recently abstinent methamphetamine users and 15 healthy controls completed two laboratory paradigms of 'simulated' drug choice (choice for drug-related vs affectively pleasant, unpleasant, and neutral images), and underwent positron emission tomography measurements of dopamine D2-type receptor availability, indicated by binding potential (BPND) for [18F]fallypride. Thirteen of the methamphetamine users and 10 controls also underwent [11C]NNC112 PET scans to measure dopamine D1-type receptor availability. Group analyses showed that, compared with controls, methamphetamine users chose to view more methamphetamine-related images on one task, with a similar trend on the second task. Regression analyses showed that, on both tasks, the more methamphetamine users chose to view methamphetamine images, specifically vs pleasant images (the most frequently chosen images across all participants), the lower was their D2-type BPND in the lateral orbitofrontal cortex, an important region in value-based choice. No associations were observed with D2-type BPND in striatal regions, or with D1-type BPND in any region. These results identify a neurochemical correlate for a laboratory drug-seeking paradigm that can be administered to treatment-seeking and abstaining drug-addicted individuals. More broadly, these results refine the central hypothesis that dopamine-system deficits contribute to drug-biased decision-making in addiction, here showing a role for the orbitofrontal cortex.

Visual space is perceived as continuous and stable even though visual inputs from the left and right visual fields are initially processed separately within the two cortical hemispheres. In the research reported here, we examined whether the visual system utilizes a dynamic recalibration mechanism to integrate these representations and to maintain alignment across the visual fields. Subjects adapted to randomly oriented moving lines that straddled the vertical meridian; these lines were vertically offset between the left and right hemifields. Subsequent vernier alignment judgments revealed a negative aftereffect: An offset in the same direction as the adaptation was required to correct the perceived misalignment. This aftereffect was specific to adaptation to vertical, but not horizontal, misalignments and also occurred following adaptation to movie clips and patterns without coherent motion. Our results demonstrate that the visual system unifies the left and right halves of visual space by continuously recalibrating the alignment of elements across the visual fields.

Covert motor learning can sometimes transfer to overt behavior. We investigated the neural mechanism underlying transfer by constructing a two-context paradigm. Subjects performed cursor movements either overtly using arm movements, or covertly via a brain-machine interface that moves the cursor based on motor cortical activity (in lieu of arm movement). These tasks helped evaluate whether and how cortical changes resulting from "covert rehearsal" affect overt performance. We found that covert learning indeed transfers to overt performance and is accompanied by systematic population-level changes in motor preparatory activity. Current models of motor cortical function ascribe motor preparation to achieving initial conditions favorable for subsequent movement-period neural dynamics. We found that covert and overt contexts share these initial conditions, and covert rehearsal manipulates them in a manner that persists across context changes, thus facilitating overt motor learning. This transfer learning mechanism might provide new insights into other covert processes like mental rehearsal.

Understanding another's actions, including what they are doing and why they are doing it, can be difficult for individuals with autism spectrum disorder (ASD). This understanding is supported by the action observation (AON) and mentalizing (MZN) networks, as well as the superior temporal sulcus. We examined these areas in children with ASD and typically developing controls by having participants view eating and placing actions performed in conventional and unconventional ways while functional magnetic resonance images were collected. We found an effect of action-type, but not conventionality, in both groups, and a between groups difference only when viewing conventional eating actions. Findings suggest there are not global AON/MZN deficits in ASD, and observing unconventional actions may not spontaneously activate the MZN.

We used local field potentials (LFPs) and spikes to investigate representations of visual space in prefrontal cortex and the dynamics of those representations during eye movements. Spatial information contained in LFPs of the frontal eye field (FEF) was differentially distributed across frequencies, with a majority of that information being carried in alpha and high-gamma bands and minimal signal in the low-gamma band. During fixation, spatial information from alpha and high-gamma bands and spiking activity was robust across cortical layers. Receptive fields (RFs) derived from alpha and high-gamma bands were retinocentrically organized, and they were spatially correlated both with each other and with spiking RFs. However, alpha and high-gamma RFs probed before eye movements were dissociated. Whereas high-gamma and spiking RFs immediately converged toward the movement goal, alpha RFs remained largely unchanged during the initial probe response, but they converged later. These observations reveal possible mechanisms of dynamic spatial representations that underlie visual perception during eye movements.

During threat of shock, the startle reflex is potentiated, suggesting modulation by defensive mobilization. To determine whether startle potentiation is specific to aversive anticipation, startle reflexes were measured in the context of either aversive or appetitive anticipation in a between-subject study. Participants wore a device on the wrist that could deliver electrical shock (n = 49), or vibrotactile stimulation indicating monetary reward (n = 48). Cues signaling threat or safe periods were presented alone, or accompanied by presentation of affective and neutral pictures on half of the trials. Results indicated that the startle reflex was significantly potentiated when anticipating either shock or reward, compared to safe periods, both when no picture was presented, as well as during picture viewing. The difference between threat and safety in both reflex magnitude and skin conductance changes was larger for those anticipating shock, suggesting that the aversive context was more motivationally engaging. The pattern of reflex modulation as a function of picture valence varied under threat and safety, but was identical in the shock and reward groups, consistent with a hypothesis that anticipation of either aversive or appetitive events prompts heightened perceptual vigilance, potentiating the acoustic startle reflex.

BACKGROUND:Symptoms of psychosis in schizophrenia reflect disturbances in sense of agency-difficulty distinguishing internally from externally generated sensory and perceptual experiences. One theory attributes these anomalies to a disruption in corollary discharge (CD), an internal copy of generated motor commands used to distinguish self-movement-generated sensations from externally generated stimulation. METHODS:We used a transsaccadic shift detection paradigm to examine possible deficits in CD and sense of agency based on the ability to perceive visual changes in 31 schizophrenia patients (SZPs) and 31 healthy control subjects. We derived perceptual measures based on manual responses indicating the transsaccadic target shift direction. We also developed a distance-from-unity-line measure to quantify use of CD versus purely sensory (visual) information in evaluating visual changes in the environment after an eye movement. RESULTS:SZPs had higher perceptual thresholds in detecting shift of target location than healthy control subjects, regardless of movement direction or amplitude. Despite producing similar hypometric saccades, healthy control subjects overestimated target location, whereas SZPs relied more on the experienced visual error and consequently underestimated the target position. We show that in SZPs the postsaccadic judgment of the initial target location was largely aligned with the measure based only on visual error, suggesting a deficit in the use of CD. This CD deficit also correlated with positive schizophrenia symptoms and disturbances in sense of agency. CONCLUSIONS:These results provide a novel approach in quantifying abnormal use of CD in SZPs and provide a framework to distinguish deficits in sensory processing versus defects in the internal CD-based monitoring of movement.

Recent research suggests that attributing human movement to ambiguous and static Rorschach stimuli (M responses) is associated with EEG mu suppression, and that disrupting the left inferior gyrus (LIFG; a putative area implicated in mirroring activity) decreases the tendency to see human movement when exposed to the Rorschach ambiguous stimuli. The current study aimed to test whether disrupting the LIFG via repetitive transcranial stimulation (rTMS) would decrease both the number of human movement attributions and EEG mu suppression. Each participant was exposed to the Rorschach stimuli twice, i.e., during a baseline condition (without rTMS but with EEG recording) and soon after rTMS (TMS condition with EEG recording). Experimental group (N = 15) was stimulated over the LIFG, while the control group (N = 13) was stimulated over the Vertex. As expected, disrupting the LIFG but not Vertex, decreased the number of M attributions provided by the participants exposed to the Rorschach stimuli, with a significant interaction effect. Unexpectedly, however, rTMS did not significantly influence EEG mu suppression.

Mice use vision to navigate and avoid predators in natural environments. However, their visual systems are compact compared to other mammals, and it is unclear how well mice can discriminate ethologically relevant scenes. Here, we examined natural scene discrimination in mice using an automated touch-screen system. We estimated the discrimination difficulty using the computational metric structural similarity (SSIM), and constructed psychometric curves. However, the performance of each mouse was better predicted by the mean performance of other mice than SSIM. This high inter-mouse agreement indicates that mice use common and robust strategies to discriminate natural scenes. We tested several other image metrics to find an alternative to SSIM for predicting discrimination performance. We found that a simple, primary visual cortex (V1)-inspired model predicted mouse performance with fidelity approaching the inter-mouse agreement. The model involved convolving the images with Gabor filters, and its performance varied with the orientation of the Gabor filter. This orientation dependence was driven by the stimuli, rather than an innate biological feature. Together, these results indicate that mice are adept at discriminating natural scenes, and their performance is well predicted by simple models of V1 processing.

In subjects with alternating strabismus, either eye can be used to saccade to visual targets. The brain must calculate the correct vector for each saccade, which will depend on the eye chosen to make it. The superior colliculus, a major midbrain center for saccade generation, was examined to determine whether the maps serving each eye were shifted to compensate for strabismus. Alternating exotropia was induced in two male macaques at age 1 month by sectioning the tendons of the medial recti. Once the animals grew to maturity, they were trained to fixate targets with either eye. Receptive fields were mapped in the superior colliculus using a sparse noise stimulus while the monkeys alternated fixation. For some neurons, sparse noise was presented dichoptically to probe for anomalous retinal correspondence. After recordings, microstimulation was applied to compare sensory and motor maps. The data showed that receptive fields were offset in position by the ocular deviation, but otherwise remained aligned. In one animal, the left eye's coordinates were rotated ∼20° clockwise with respect to those of the right eye. This was explained by a corresponding cyclorotation of the ocular fundi, which produced an A-pattern deviation. Microstimulation drove the eyes accurately to the site of receptive fields, as in normal animals. Single-cell recordings uncovered no evidence for anomalous retinal correspondence. Despite strabismus, neurons remained responsive to stimulation of either eye. Misalignment of the eyes early in life does not alter the organization of topographic maps or disrupt binocular convergence in the superior colliculus.SIGNIFICANCE STATEMENT Patients with strabismus are able to make rapid eye movements, known as saccades, toward visual targets almost as gracefully as subjects with normal binocular alignment. They can even exercise the option of using the right eye or the left eye. It is unknown how the brain measures the degree of ocular misalignment and uses it to compute the appropriate saccade for either eye. The obvious place to investigate is the superior colliculus, a midbrain oculomotor center responsible for the generation of saccades. Here, we report the first experiments in the superior colliculus of awake primates with strabismus using a combination of single-cell recordings and microstimulation to explore the organization of its topographic maps.

There is much evidence that neural activity in the human brain is modulated by task difficulty, particularly in visual, frontal, and parietal cortices. However, some basic psychophysical tasks in visual perception do not give rise to this expected effect, at least not in the visual cortex. In the current study, we used functional magnetic resonance imaging (fMRI) to record brain activity while systematically manipulating task difficulty in a motion discrimination task, by varying the angular difference between the motion direction of random dots and a reference direction. We used both a blocked and an event-related design, and presented stimuli in both central and peripheral vision. The behavioral psychometric function, across angular differences of 3°, 9°, 15°, or 80°, spanned the full response range, as expected. The mean blood oxygen level dependent (BOLD) signals were also correlated within-participants between the blocked and event-related designs, across all brain areas tested. Within the visual cortex, the voxel response patterns correlated more within-conditions (e.g., 3° and 3°) than between-conditions (e.g., 3° and 9°), in both designs, further attesting to the reasonable quality of the BOLD data. Nevertheless, the BOLD-o-metric functions (i.e., BOLD activity as a function of task difficulty) were flat in the whole-brain and region-of-interest (ROI) analyses, including in the visual cortex, the parietal cortex, in both designs, and in foveal and peripheral visual fields alike. Indeed, there was little difference between BOLD activity during the 3° and 80° conditions. Some suggestive evidence of difficulty modulation was revealed only in the superior and inferior frontal gyri for the blocked design. We conclude that, in motion discrimination, there is no systematic BOLD modulation that accompanies the standard psychometric function across different hierarchies of cortical areas, except for the frontal lobe of the brain.

Our capacity to attend a target while ignoring irrelevant distraction impacts our ability to successfully interact with our environment. Previous reports have sometimes identified excessive distractor interference in both autism and schizophrenia spectrum disorders and in neurotypical individuals with high subclinical expressions of these conditions. Independent of task, we show that the direction of the effect of autism or psychosis traits on the suppression or rejection of a non-target item is diametrical. In Study 1, in which the presence of a salient non-target item hindered performance, higher autism traits were associated with better performance, while higher psychosis traits were associated with worse performance. In Study 2, in which the presence of a salient non-target item facilitated performance, a complete reversal of effects was observed. Future clinical interventions may be informed by the context-specific advantages we observed for the autism and psychosis spectra, and by the need to consider the diametric effects they yield.

Episodic memory is a critical capacity that involves remembering past events along with their spatial and temporal contexts. Relatively little is known about the relations between spatial and temporal information in long-term memory in children or adults. The present research examined the influence of the mental timeline (linear horizontal display extending from the left to right direction for English speakers) on memory for events and their spatial and temporal features in 7-year-olds, 9-year-olds, 11-year-olds and young adults (N = 146). During encoding, participants studied triplets of objects, varying on two dimensions of the mental timeline: linearity (whether objects were presented in linear succession or not) and direction (whether objects were presented from left-to-right or right-to-left). After a delay, during retrieval, participants were tested on their memory for individual objects, and either the spatial location or temporal order of the objects. We found that overall accuracy for spatial location was higher than accuracy for temporal order, and there was a parallel developmental trajectory for both these aspects of memory. Across age groups we found that memory for temporal order, but not spatial location, was influenced by linearity and direction (i.e., match to mental timeline). Thus, in both children and adults the spatiotemporal mental timeline supported memory for temporal order, converging with predictions generated within domains of language and thought and enhancing our understanding of how space and time are represented in the mind.

The current research explored toddlers' gaze fixation during a scene showing a person expressing sadness after a ball is stolen from her. The relation between the duration of gaze fixation on different parts of the person's sad face (e.g., eyes, mouth) and theory of mind skills was examined. Eye tracking data indicated that before the actor experienced the negative event, toddlers divided their fixation equally between the actor's happy face and other distracting objects, but looked longer at the face after the ball was stolen and she expressed sadness. The strongest predictor of increased focus on the sad face versus other elements of the scene was toddlers' ability to predict others' emotional reactions when outcomes fulfilled (happiness) or failed to fulfill (sadness) desires, whereas toddlers' visual perspective-taking skills predicted their more specific focusing on the actor's eyes and, for boys only, mouth. Furthermore, gender differences emerged in toddlers' fixation on parts of the scene. Taken together, these findings suggest that top-down processes are involved in the scanning of emotional facial expressions in toddlers.