Functional specializations for music processing in the human newborn brain

In adults, specific neural systems with right-hemispheric weighting are necessary to process pitch, melody, and harmony as well as structure and meaning emerging from musical sequences. It is not known to what extent the specialization of these systems results from long-term exposure to music or from neurobiological constraints. One way to address this question is to examine how these systems function at birth, when auditory experience is minimal. We used functional MRI to measure brain activity in 1- to 3-day-old newborns while they heard excerpts of Western tonal music and altered versions of the same excerpts. Altered versions either included changes of the tonal key or were permanently dissonant. Music evoked predominantly right-hemispheric activations in primary and higher order auditory cortex. During presentation of the altered excerpts, hemodynamic responses were significantly reduced in the rig1ht auditory cortex, and activations emerged in the left inferior frontal cortex and limbic structures. These results demonstrate that the infant brain shows a hemispheric specialization in processing music as early as the first postnatal hours. Results also indicate that the neural architecture underlying music processing in newborns is sensitive to changes in tonal key as well as to differences in consonance and dissonance.     

Interspecies activation correlations reveal functional correspondences between marmoset and human brain areas

The common marmoset has enormous promise as a nonhuman primate model of human brain functions. While resting-state functional MRI (fMRI) has provided evidence for a similar organization of marmoset and human cortices, the technique cannot be used to map the functional correspondences of brain regions between species. This limitation can be overcome by movie-driven fMRI (md-fMRI), which has become a popular tool for noninvasively mapping the neural patterns generated by rich and naturalistic stimulation. Here, we used md-fMRI in marmosets and humans to identify whole-brain functional correspondences between the two primate species. In particular, we describe functional correlates for the well-known human face, body, and scene patches in marmosets. We find that these networks have a similar organization in both species, suggesting a largely conserved organization of higher-order visual areas between New World marmoset monkeys and humans. However, while face patches in humans and marmosets were activated by marmoset faces, only human face patches responded to the faces of other animals. Together, the results demonstrate that higher-order visual processing might be a conserved feature between humans and New World marmoset monkeys but that small, potentially important functional differences exist.

The common marmoset has become an important nonhuman primate model for bridging the translational gap between rodents and humans. Marmosets have a lissencephalic cortex, like rodents, but as primates, they possess a complex visual system (1) and exhibit a similar visuomotor behavior as macaques and humans (2, 3). This, paired with a high reproductive power, small size, and fast maturation rate, make this nonhuman primate (NHP) species particularly interesting for neuroscience.To identify and compare the functional architecture of the primate brain, functional MRI (fMRI) has often been applied because of its noninvasive measures and whole brain coverage (4, 5). In particular, resting-state fMRI (RS-fMRI) has been used 1) to identify homologous large-scale brain networks between marmosets and humans (6, 7), 2) to define functional boundaries based on intrinsic functional connectivity (8, 9), and 3) to use functional connectivity “fingerprints” of brain areas to establish similarities between marmosets, rodents, and humans (10). Because resting-state patterns are state agnostic and spontaneous, however, this technique cannot be used to map the functional correspondences of interspecies blood oxygen level–dependent (BOLD) fluctuations over time. Task-based fMRI is better suited for mapping stimuli-driven fluctuations across species, and, indeed, a few studies have used task-based fMRI in awake marmosets to identify areas related to specific functions [e.g., visuosaccadic orienting (11), processing of faces and bodies (12, 13), looming and receding visual stimuli (14), and tactile processing (15)]. A major drawback of task-based fMRI is that compliance is often poor in NHPs and that each task can only reveal the limited set of functional activations for which it was designed.These limitations can be overcome by employing movie stimuli, which provide rich and naturalistic stimulations. Human studies have shown that movie-driven fMRI (md-fMRI) responses are highly selective between brain regions, engage many brain regions, and are highly reliable between subjects (16–19). Functional correspondences between species can be directly tested by the interspecies activity correlation (ISAC) method, which uses the md-fMRI time course in a seed region in one species to identify functional correspondences across the cortex of the other species. This technique has been successfully employed to identify functional correspondences (analogies) between human and macaque cortical areas (20), but this powerful mapping technique has yet to be applied to the marmoset brain.Here, we used md-fMRI to compare directly the brain activations between marmosets and humans and to establish functional correspondences between cortical areas across the brain in the two species. We focused our analysis on identifying analogies of the well-known human face-, body-, and scene-selective networks in the marmoset brain. Not only do these networks play pivotal roles in complex primate vision, face- and body-selective areas have also been described by a few task-based fMRI studies in marmosets (12, 13), providing an independent validation for some of these results.     

Functional specificity for high-level linguistic processing in the human brain

Neuroscientists have debated for centuries whether some regions of the human brain are selectively engaged in specific high-level mental functions or whether, instead, cognition is implemented in multifunctional brain regions. For the critical case of language, conflicting answers arise from the neuropsychological literature, which features striking dissociations between deficits in linguistic and nonlinguistic abilities, vs. the neuroimaging literature, which has argued for overlap between activations for linguistic and nonlinguistic processes, including arithmetic, domain general abilities like cognitive control, and music. Here, we use functional MRI to define classic language regions functionally in each subject individually and then examine the response of these regions to the nonlinguistic functions most commonly argued to engage these regions: arithmetic, working memory, cognitive control, and music. We find little or no response in language regions to these nonlinguistic functions. These data support a clear distinction between language and other cognitive processes, resolving the prior conflict between the neuropsychological and neuroimaging literatures.     

Prestimulus functional connectivity determines pain perception in humans

Pain is a highly subjective experience that can be substantially influenced by differences in individual susceptibility as well as personality. How susceptibility to pain and personality translate to brain activity is largely unknown. Here, we report that the functional connectivity of two key brain areas before a sensory event reflects the susceptibility to a subsequent noxious stimulus being perceived as painful. Specifically, the prestimulus connectivity among brain areas related to the subjective perception of the body and to the modulation of pain (anterior insular cortex and brainstem, respectively) determines whether a noxious event is perceived as painful. Further, these effects of prestimulus connectivity on pain perception covary with pain-relevant personality traits. More anxious and pain-attentive individuals display weaker descending connectivity to pain modulatory brain areas. We conclude that variations in functional connectivity underlie personality-related differences in individual susceptibility to pain.     

Encoding of 3D physical dimensions by face-selective cortical neurons

Neurons throughout the primate inferior temporal (IT) cortex respond selectively to visual images of faces and other complex objects. The response magnitude of neurons to a given image often depends on the size at which the image is presented, usually on a flat display at a fixed distance. While such size sensitivity might simply reflect the angular subtense of retinal image stimulation in degrees, one unexplored possibility is that it tracks the real-world geometry of physical objects, such as their size and distance to the observer in centimeters. This distinction bears fundamentally on the nature of object representation in IT and on the scope of visual operations supported by the ventral visual pathway. To address this question, we assessed the response dependency of neurons in the macaque anterior fundus (AF) face patch to the angular versus physical size of faces. We employed a macaque avatar to stereoscopically render three-dimensional (3D) photorealistic faces at multiple sizes and distances, including a subset of size/distance combinations designed to cast the same size retinal image projection. We found that most AF neurons were modulated principally by the 3D physical size of the face rather than its two-dimensional (2D) angular size on the retina. Further, most neurons responded strongest to extremely large and small faces, rather than to those of normal size. Together, these findings reveal a graded encoding of physical size among face patch neurons, providing evidence that category-selective regions of the primate ventral visual pathway participate in a geometric analysis of real-world objects.

We experience the world in three-dimensional (3D) space, perceiving and interacting with objects and individuals in a scene. For humans and other primates, much of this experience is served by vision, with broad stretches of the cerebral cortex ostensibly devoted to making visual sense of the world. For example, individual neurons throughout the inferior temporal (IT) cortex of the macaque respond selectively to meaningful objects, with neurons of similar response properties often aggregated in functional clusters (1–3). One striking finding about the object selectivity of IT neurons is its tolerance to natural image transformations, such as scaling and translation (4–12). Namely, if stimuli are ranked based on the responses they elicit from a given neuron, this ranking often remains unchanged when stimuli are translated on the screen or scaled up or down several-fold in size. Scale tolerance in object selectivity is thought to reflect the capacity of the brain to compute a conceptual or abstracted representation of the retinal image separate from its metric details. While the mechanism underlying this apparently intrinsic feature of ventral stream visual processing is poorly understood, it is thought to be critical for image-based object recognition (4, 13–17).At the same time, scaling an image up or down can greatly change the responses of IT neurons to stimuli, even as the rank-order selectivity to stimuli is preserved (18–20). This size-dependent rate modulation is poorly understood and seldom considered explicitly. One relatively unexplored possibility is that some IT neurons encode the physical dimensions of objects, in addition to their shape, and their featural, and semantic properties. The explicit coding of parameters such as absolute object size and distance from the observer might facilitate visual operations concerned with the perception of scene geometry and interaction with the local environment. Additionally, the brain may benefit by retaining internal metric information about the typical sizes of objects (21, 22), as this information could be applied to subsequent perceptual judgments about objects and individuals in the context of natural visual behaviors (23).The visual encoding of 3D space is usually associated with parietal cortex in the dorsal visual pathway, where coordinate transformations are thought to convert retinal signals to 3D information about objects and the environment that can be used to guide effector actions (24). However, a few studies have demonstrated that neurons in the ventral pathway also exhibit signals related to 3D spatial perception. For example, in area V4 neural responses to a given retinal image are modulated based on the physical distance at which that image is presented (25) as well as volumetric 3D shape parameters (26). At later ventral pathway processing stages, the superior temporal sulcus (STS) is marked by selectivity to 3D object shape, potentially reflecting their interplay with intraparietal areas concerned with 3D visual geometry (27–32). While these findings demonstrate that 3D information influences responses across the ventral visual pathway, little is known about whether these areas explicitly encode the physical dimensions of objects, such as their size or distance from the observer.Here we explicitly investigate how a population of category-selective neurons in macaque IT encode the physical dimensions of objects. We recorded from the anterior fundus (AF) face patch (33), a well-studied face-selective region of the STS where neurons are known to be both selective for faces and sensitive to their spatial scale (34). We asked whether such scale sensitivity primarily reflects the 2D image of a face on the retina or the 3D physical geometry of the face and head in the real world. In most visual electrophysiology experiments, the retinal and physical geometry of an image are yoked: scaling an image on a display alters both its physical size and its retinal subtense. Moreover, absent other explicit depth cues, an image has ambiguous depth and thus cannot be uniquely mapped to the 3D world. In the present study, we used a recently developed macaque avatar model (35) to stereoscopically render photorealistic 3D faces of unambiguous physical size and distance. We found that the size sensitivity of most AF neurons was dictated primarily by the physical dimensions of a face rather than by its angular subtense on the retina. We further discovered that neural responses were strongest to extreme-sized faces rather than normal sized faces, opposing intuition but consistent with ideas of predictive coding. We discuss how object-selective IT neurons might contribute to important and conserved elements of natural visual behavior through their encoding of real-world geometric parameters.     

Imaging prior information in the brain

In making sense of the visual world, the brain's processing is driven by two factors: the physical information provided by the eyes ("bottom-up" data) and the expectancies driven by past experience ("top-down" influences). We use degraded stimuli to tease apart the effects of bottom-up and top-down processes because they are easier to recognize with prior knowledge of undegraded images. Using machine learning algorithms, we quantify the amount of information that brain regions contain about stimuli as the subject learns the coherent images. Our results show that several distinct regions, including high-level visual areas and the retinotopic cortex, contain more information about degraded stimuli with prior knowledge. Critically, these regions are separate from those that exhibit classical priming, indicating that top-down influences are more than feature-based attention. Together, our results show how the neural processing of complex imagery is rapidly influenced by fleeting experiences.     

Spectral quality of light modulates emotional brain responses in humans

Light therapy can be an effective treatment for mood disorders, suggesting that light is able to affect mood state in the long term. As a first step to understand this effect, we hypothesized that light might also acutely influence emotion and tested whether short exposures to light modulate emotional brain responses. During functional magnetic resonance imaging, 17 healthy volunteers listened to emotional and neutral vocal stimuli while being exposed to alternating 40-s periods of blue or green ambient light. Blue (relative to green) light increased responses to emotional stimuli in the voice area of the temporal cortex and in the hippocampus. During emotional processing, the functional connectivity between the voice area, the amygdala, and the hypothalamus was selectively enhanced in the context of blue illumination, which shows that responses to emotional stimulation in the hypothalamus and amygdala are influenced by both the decoding of vocal information in the voice area and the spectral quality of ambient light. These results demonstrate the acute influence of light and its spectral quality on emotional brain processing and identify a unique network merging affective and ambient light information.     

Leptin replacement alters brain response to food cues in genetically leptin-deficient adults

A missense mutation in the ob gene causes leptin deficiency and morbid obesity. Leptin replacement to three adults with this mutation normalized body weight and eating behavior. Because the neural circuits mediating these changes were unknown, we paired functional magnetic resonance imaging (fMRI) with presentation of food cues to these subjects. During viewing of food-related stimuli, leptin replacement reduced brain activation in regions linked to hunger (insula, parietal and temporal cortex) while enhancing activation in regions linked to inhibition and satiety (prefrontal cortex). Leptin appears to modulate feeding behavior through these circuits, suggesting therapeutic targets for human obesity.     

Long-term effects of marijuana use on the brain

Questions surrounding the effects of chronic marijuana use on brain structure continue to increase. To date, however, findings remain inconclusive. In this comprehensive study that aimed to characterize brain alterations associated with chronic marijuana use, we measured gray matter (GM) volume via structural MRI across the whole brain by using voxel-based morphology, synchrony among abnormal GM regions during resting state via functional connectivity MRI, and white matter integrity (i.e., structural connectivity) between the abnormal GM regions via diffusion tensor imaging in 48 marijuana users and 62 age- and sex-matched nonusing controls. The results showed that compared with controls, marijuana users had significantly less bilateral orbitofrontal gyri volume, higher functional connectivity in the orbitofrontal cortex (OFC) network, and higher structural connectivity in tracts that innervate the OFC (forceps minor) as measured by fractional anisotropy (FA). Increased OFC functional connectivity in marijuana users was associated with earlier age of onset. Lastly, a quadratic trend was observed suggesting that the FA of the forceps minor tract initially increased following regular marijuana use but decreased with protracted regular use. This pattern may indicate differential effects of initial and chronic marijuana use that may reflect complex neuroadaptive processes in response to marijuana use. Despite the observed age of onset effects, longitudinal studies are needed to determine causality of these effects.The rate of marijuana use has had a steady increase since 2007 (1). Among >400 chemical compounds, marijuana’s effects are primarily attributed to δ-9-tetrahydrocannabinol (THC), which is the main psychoactive ingredient in the cannabis plant. THC binds to cannabinoid receptors, which are ubiquitous in the brain. Consequently, exposure to THC leads to neural changes affecting diverse cognitive processes. These changes have been observed to be long-lasting, suggesting that neural changes due to marijuana use may affect neural architecture (2). However, to date, these brain changes as a result of marijuana use remains equivocal. Specifically, although functional changes have been widely reported across cognitive domains in both adult and adolescent cannabis users (3–6), structural changes associated with marijuana use have not been consistent. Although some have reported decreases in regional brain volume such as in the hippocampus, orbitofrontal cortex, amygdala, and striatum (7–12), others have reported increases in amygdala, nucleus accumbens, and cerebellar volumes in chronic marijuana users (13–15). However, others have reported no observable difference in global or regional gray or white matter volumes in chronic marijuana users (16, 17). These inconsistencies could be attributed to methodological differences across studies pertaining to study samples (e.g., severity of marijuana use, age, sex, comorbidity with other substance use or psychiatric disorders) and/or study design (e.g., study modality, regions of interest).Because THC binds to cannabinoid 1 (CB1) receptors in the brain, when differences are observed, these morphological changes associated with marijuana use have been reported in CB1 receptor-enriched areas such as the orbitofrontal cortex, anterior cingulate, striatum, amygdala, insula, hippocampus, and cerebellum (2, 11, 13, 18). CB1 receptors are widely distributed in the neocortex, but more restricted in the hindbrain and the spinal cord (19). For example, in a recent study by Battistella et al. (18), they found significant brain volume reductions in the medial temporal cortex, temporal pole, parahippocampal gyrus, insula, and orbitofrontal cortex (OFC) in regular marijuana users compared with occasional users. Whether these reductions in brain volume lead to downstream changes in brain organization and function, however, is still unknown.Nevertheless, emergent studies have demonstrated a link between brain structure and connectivity. For example, Van den Heuvel et al. and Greicius et al. demonstrated robust structural connections between white matter indexes and functional connectivity strength within the default mode network (20, 21). Similarly, others have reported correlated patterns of gray matter structure and connectivity that are in many ways reflective of the underlying intrinsic networks (22). Thus, given the literature suggesting a direct relationship between structural and functional connectivity, it is likely that connectivity changes would also be present where alterations in brain volume are observed as a result of marijuana use.The goal of this study was to characterize alterations in brain morphometry and determine potential downstream effects in connectivity as a result of chronic marijuana use. To address the existing inconsistencies in the literature that may be in part due to methodological issues, we (i) used three different MRI techniques to investigate a large cohort of well-characterized chronic cannabis users with a wide age range (allowing for characterization without developmental or maturational biases) and compared them to age- and sex-matched nonusing controls; (ii) examined observable global (rather than select) gray matter differences between marijuana users and nonusing controls; and (iii) performed subsequent analyses to determine how these changes relate to functional and structural connectivity, as well as behavior. Given the existing literature on morphometric reductions associated with long-term marijuana use, we expected gray matter reductions in THC-enriched areas in chronic marijuana users that will be associated with changes in brain connectivity and marijuana-related behavior.     

Topographic organization of macaque area LIP

Despite several attempts to define retinotopic maps in the macaque lateral intraparietal area (LIP) using histological, electrophysiological, and neuroimaging methods, the degree to which this area is topographically organized remains controversial. We recorded blood oxygenation level–dependent signals with functional MRI from two macaques performing a difficult visual search task on stimuli presented at the fovea or in the periphery of the visual field. The results revealed the presence of a single topographic representation of the contralateral hemifield in the ventral subdivision of the LIP (LIPv) in both hemispheres of both monkeys. Also, a foveal representation was localized in rostral LIPv rather than in dorsal LIP (LIPd) as previous experiments had suggested. Finally, both LIPd and LIPv responded only to contralateral stimuli. In contrast, human studies have reported multiple topographic maps in intraparietal cortex and robust responses to ipsilateral stimuli. These blood oxygenation level–dependent functional MRI results provide clear evidence for the topographic organization of macaque LIP that complements the results of previous electrophysiology studies, and also reveal some unexpected characteristics of this organization that have eluded these previous studies. The results also delineate organizational differences between LIPv and LIPd, providing support for these two histologically defined areas may subserve different visuospatial functions. Finally, these findings point to potential evolutionary differences in functional organization with human posterior parietal cortex.     

Neurophysiological origin of human brain asymmetry for speech and language

The physiological basis of human cerebral asymmetry for language remains mysterious. We have used simultaneous physiological and anatomical measurements to investigate the issue. Concentrating on neural oscillatory activity in speech-specific frequency bands and exploring interactions between gestural (motor) and auditory-evoked activity, we find, in the absence of language-related processing, that left auditory, somatosensory, articulatory motor, and inferior parietal cortices show specific, lateralized, speech-related physiological properties. With the addition of ecologically valid audiovisual stimulation, activity in auditory cortex synchronizes with left-dominant input from the motor cortex at frequencies corresponding to syllabic, but not phonemic, speech rhythms. Our results support theories of language lateralization that posit a major role for intrinsic, hardwired perceptuomotor processing in syllabic parsing and are compatible both with the evolutionary view that speech arose from a combination of syllable-sized vocalizations and meaningful hand gestures and with developmental observations suggesting phonemic analysis is a developmentally acquired process.     

A mechanistic account of value computation in the human brain

To make decisions based on the value of different options, we often have to combine different sources of probabilistic evidence. For example, when shopping for strawberries on a fruit stand, one uses their color and size to infer—with some uncertainty—which strawberries taste best. Despite much progress in understanding the neural underpinnings of value-based decision making in humans, it remains unclear how the brain represents different sources of probabilistic evidence and how they are used to compute value signals needed to drive the decision. Here, we use a visual probabilistic categorization task to show that regions in ventral temporal cortex encode probabilistic evidence for different decision alternatives, while ventromedial prefrontal cortex integrates information from these regions into a value signal using a difference-based comparator operation.     

Acuity-independent effects of visual deprivation on human visual cortex

Visual development depends on sensory input during an early developmental critical period. Deviation of the pointing direction of the two eyes (strabismus) or chronic optical blur (anisometropia) separately and together can disrupt the formation of normal binocular interactions and the development of spatial processing, leading to a loss of stereopsis and visual acuity known as amblyopia. To shed new light on how these two different forms of visual deprivation affect the development of visual cortex, we used event-related potentials (ERPs) to study the temporal evolution of visual responses in patients who had experienced either strabismus or anisometropia early in life. To make a specific statement about the locus of deprivation effects, we took advantage of a stimulation paradigm in which we could measure deprivation effects that arise either before or after a configuration-specific response to illusory contours (ICs). Extraction of ICs is known to first occur in extrastriate visual areas. Our ERP measurements indicate that deprivation via strabismus affects both the early part of the evoked response that occurs before ICs are formed as well as the later IC-selective response. Importantly, these effects are found in the normal-acuity nonamblyopic eyes of strabismic amblyopes and in both eyes of strabismic patients without amblyopia. The nonamblyopic eyes of anisometropic amblyopes, by contrast, are normal. Our results indicate that beyond the well-known effects of strabismus on the development of normal binocularity, it also affects the early stages of monocular feature processing in an acuity-independent fashion.Over 50 y of research on experimental animal models has indicated that deprivation of normal visual experience during a developmental critical period perturbs both the structure and function of primary visual cortex (1–4). The animal models were developed to understand the underlying neural mechanisms of amblyopia, a common human developmental disorder of spatial vision associated with the presence of strabismus, anisometropia, or form deprivation during early life (5). Amblyopia is classically defined on the basis of poor visual acuity, but many other visual functions are known to be affected (6–8).The earliest experimental studies of visual deprivation focused on the effects of monocular lid suture, and these studies showed devastating effects on the ability of the deprived eye to drive neural responses, retain synaptic connections, and guide visual behavior (9–11). Later work studied less extreme forms of deprivation that are common in humans, such as the effects of strabismus (deviation of the pointing direction of the two eyes) (12, 13) or anisometropia (chronic optical blur) (14, 15). More recent studies (16, 17) have found that losses in cell responses in primary visual cortex appear to be insufficient to explain the magnitude of behaviorally measured deficits. Based on these results, a hypothesis has been put forward that these forms of deprivation have their primary effects in extrastriate cortex (16).Motivated by this idea, psychophysicists have sought evidence that extrastriate cortex is particularly impaired in human amblyopia. This work has used tasks whose execution is fundamentally limited by processing resources that single-cell physiology suggests are located in extrastriate cortex. As a second step, these studies have scaled stimuli based on visual acuity and compensated for contrast sensitivity losses to equate the output of early visual cortex from the amblyopic eye to that of normal-vision participants. Despite a nominal match at the level of early visual cortex outputs, patients with amblyopia still show deficits on illusory tilt perception (18), contour integration (19–23), global motion sensitivity (8, 24–28), object enumeration (29), and object tracking (7, 30). The impairments listed above have been interpreted to indicate that amblyopia may involve abnormalities in “higher-level” (e.g., extrastriate) neural processing that occur independent of any deficits in early processing stages (e.g., in striate cortex). A limitation of the existing psychophysical approaches has been the need to make an assumption that the stimulus scaling used to equate stimuli for visibility fully equilibrates the activity of early visual cortex. It would be preferable to take an approach that allows one to measure neural responses directly from both early and later stages of visual processing. Here we use event-related potentials (ERPs) and a stimulation paradigm that allow us to record responses from both early visual cortex and higher-level, extrastriate areas.Our approach is similar in spirit to existing psychophysical approaches: We use a stimulus configuration—illusory contours (ICs)—that previous single-unit studies have shown to be first extracted in extrastriate cortex (31–34). ICs, also referred to as subjective contours, render object borders that are perceptually vivid but that are created in the absence of luminance contrast or chrominance gradients (35). ICs have been widely used to study mechanisms of scene segmentation and grouping operations that are among the most fundamental tasks the visual system has to perform (36). ICs have garnered considerable interest because of their “inferential” nature—despite the lack of luminance edges, the visual system uses implicit configural cues to infer the presence of a contour. Finally, behavioral investigations in macaque suggest that IC perception is strongly dependent on higher visual areas, including V4 (37, 38) and inferotemporal (IT) cortex (39, 40).Instead of attempting to equate the visibility of stimuli in the amblyopic eye to that of normal control eyes, as has been typical practice in the study of amblyopia, we make a close analysis of the effects of deprivation that is based on ERP responses from the nonamblyopic eyes of patients with anisometropic or strabismic amblyopia. These eyes have normal visual acuity and normal or even supernormal contrast sensitivity (41), making the stimuli nominally equivisible without the need for scaling. We then measure evoked responses at early latencies before the time that IC selectivity arises to assess the integrity of early visual cortex, and compare these responses to those measured at longer latencies after robust IC selectivity has been established. Previous single-unit studies that have used ICs of the type used in the present study indicate that they are first extracted no later than V2 (31, 42, 43) or V4 (34). Given the difference in species and stimuli, we will refer in the following to evoked responses that lack IC sensitivity as having arisen in “early” visual cortex, rather than in specific visual areas. To further specify the site of deprivation effects, we also study a group of stereo-blind patients with strabismus who do not have amblyopia (normal visual acuity in each eye).A second goal of our study is to compare the effects of deprivation from unilateral blur (anisometropia) to that caused by strabismus. The human psychophysical literature has made a distinction in the pattern of visual loss associated with strabismus versus that associated with anisometropia (44). At least some of the differences in performance between these two types of deprivation can be explained on the level of residual stereopsis, which typically differs between these two populations (41). Whenever these two types of deprivation have been compared in terms of their effects on the monocular cell properties of V1, there has been little to differentiate the effects of the two types of deprivation (16, 45, 46). Unfortunately, there are relatively few studies of the effects of critical period deprivation on the cell-tuning properties in extrastriate cortex of any species (15, 17, 47), and there has been no comparison of the effects of strabismus vs. anisometropia in extrastriate cortex. The implication of the existing animal literature is that strabismus and anisometropia have comparable effects on early visual cortex and thus the divergence in their behavioral phenotype, as well as the major effects of deprivation, will lie in extrastriate cortex. Here we show that these two types of deprivation have differential effects very early in visual cortex, possibly as early as the transfer of information from V1 to V2.     

Connectivity reveals relationship of brain areas for reward-guided learning and decision making in human and monkey frontal cortex

Reward-guided decision-making depends on a network of brain regions. Among these are the orbitofrontal and the anterior cingulate cortex. However, it is difficult to ascertain if these areas constitute anatomical and functional unities, and how these areas correspond between monkeys and humans. To address these questions we looked at connectivity profiles of these areas using resting-state functional MRI in 38 humans and 25 macaque monkeys. We sought brain regions in the macaque that resembled 10 human areas identified with decision making and brain regions in the human that resembled six macaque areas identified with decision making. We also used diffusion-weighted MRI to delineate key human orbital and medial frontal brain regions. We identified 21 different regions, many of which could be linked to particular aspects of reward-guided learning, valuation, and decision making, and in many cases we identified areas in the macaque with similar coupling profiles.As humans we make decisions by taking into account different types of information, weighing our options carefully, and eventually coming to a conclusion. We then learn from witnessing the outcome of our decisions. Human functional MRI (fMRI) has had a major impact on elucidating the neural networks mediating decision making and learning, but key insights can only be obtained in neural recording, stimulation, and focal lesion studies conducted in animal models, such as the macaque. Combining insights from human fMRI and animal studies is, however, not straightforward because there is uncertainty about basic issues, such as anatomical and functional correspondences between species (1). For example, although there are many reports of decision value-related activity in the human ventromedial prefrontal cortex (vmPFC) (2, 3), it is unclear whether they can be related to reports of reward-related activity either on the ventromedial surface of the frontal lobe (4, 5), in the adjacent medial orbitofrontal sulcus (6), or indeed to any macaque brain area. It is claimed that some areas implicated in reward-guided decision making and learning, such as parts of anterior cingulate cortex (ACC), are not found in macaques (7), but such theories have never been formally tested.In addition, there is uncertainty about the basic constituent components of decision-making and learning circuits. To return to the example of the vmPFC, although this region is often contrasted with similarly large subdivisions of the frontal cortex, such as the lateral orbitofrontal cortex (lOFC) and ACC (8), it is unclear whether, and if so how, it should be decomposed into further subdivisions. Moreover, there are sometimes fundamental disagreements about how brain areas contribute to decision making and learning. For example, it has been claimed both that the ACC does (9–11) and does not (12) contribute to reward-based decision making and that it is concerned with distinct processes for task control, error detection, and conflict resolution (13, 14). Reliable identification and location of ACC subcomponent regions could assist the resolution of such debates.In the present study we formally compared brain regions implicated in reward-guided decision making and learning in humans and monkeys, and attempted to identify their key subdivisions in relation to function (Fig. 1). We used fMRI in 25 monkeys and 38 humans to delineate the functional interactions of “decision-making regions” with other areas in the brain while subjects were at rest. Such interactions are reliant on anatomical connections between areas (15) and determine the information an area has access to and the way it can influence other areas, and thereby behavior. Each region of the brain has a defining set of interactions, a connectional or interactional “finger-print” (16), that can be compared across species (17–19). We focused on areas throughout the entire medial and orbital frontal lobe, including the ACC, lOFC, vmPFC, and frontal pole (FP) that have been related to decision making in humans and monkeys. The results suggested areal correspondences between species, as well as finer functional fractionations within regions than previously assumed. In a second step we used a complementary technique, diffusion-weighted (DW) MRI, to confirm the existence of 21 distinct component regions within the human medial and orbitofrontal cortex. The results suggest that every day human decision making capitalizes on a neural apparatus similar to that supporting decision making in monkeys.Open in a separate windowFig. 1.(A) Overall approach of the study. fMRI analyses in 38 humans and 25 macaques were used to establish the whole-brain functional connectivity of regions in medial and orbital frontal cortex identified with reward-guided learning and decision making in the two species. The example shows the macaque brain regions that have a similar coupling profile to a human vmPFC region identified in a decision-making study (27). Reproduced from ref. 27, with permission from Macmillan Publishers Ltd, Nature Neuroscience. (B) Each region’s functional connectivity with 23 key regions was then determined and (C) summarized as a functional connectivity fingerprint. (D) Once the functional connectivity fingerprint of a human brain area was established it was compared with the functional connectivity fingerprints of 380 ROIs in macaque orbital and medial frontal cortex (one example is shown here) by calculating the summed absolute difference [the “Manhattan” or “city-block” distance (17–19) of the coupling scores]. (E) Examples of the functional connectivity fingerprints for a human (blue) and a monkey (red) brain area. Most monkey ROIs matched human areas relatively poorly and extremely good and extremely bad matches were relatively rare. We used two SDs below the mean of this distribution of summed absolute differences as a cut-off to look for “significantly” good human to monkey matches. (F) A heat map summarizing the degree of correspondence between the functional connectivity patterns of each voxel in the macaque and the human brain region shown in A. Warm red areas indicate macaque voxels that correspond most strongly. (G) Complementary parts of the investigation started with the functional connectivity fingerprints of both human (Upper) and macaque (Lower) brain areas involved in reward-guided learning and decision making and then compared them with the functional connectivity fingerprints of areas in the other species. (Top Left) Reproduced from ref. 27, with permission from Macmillan Publishers Ltd, Nature Neuroscience. (Bottom Left) Reproduced from ref. 11, with permission from Macmillan Publishers Ltd, Nature Neuroscience.     

Top-down attention switches coupling between low-level and high-level areas of human visual cortex

Top-down attention is an essential cognitive ability, allowing our finite brains to process complex natural environments by prioritizing information relevant to our goals. Previous evidence suggests that top-down attention operates by modulating stimulus-evoked neural activity within visual areas specialized for processing goal-relevant information. We show that top-down attention also has a separate influence on the background coupling between visual areas: adopting different attentional goals resulted in specific patterns of noise correlations in the visual system, whereby intrinsic activity in the same set of low-level areas was shared with only those high-level areas relevant to the current goal. These changes occurred independently of evoked activity, persisted without visual stimulation, and predicted behavioral success in deploying attention better than the modulation of evoked activity. This attentional switching of background connectivity suggests that attention may help synchronize different levels of the visual processing hierarchy, forming state-dependent functional pathways in human visual cortex to prioritize goal-relevant information.     

Spatiotemporal object continuity in human ventral visual cortex

Coherent visual experience requires that objects be represented as the same persisting individuals over time and motion. Cognitive science research has identified a powerful principle that guides such processing: Objects must trace continuous paths through space and time. Little is known, however, about how neural representations of objects, typically defined by visual features, are influenced by spatiotemporal continuity. Here, we report the consequences of spatiotemporally continuous vs. discontinuous motion on perceptual representations in human ventral visual cortex. In experiments using both dynamic occlusion and apparent motion, face-selective cortical regions exhibited significantly less activation when faces were repeated in continuous vs. discontinuous trajectories, suggesting that discontinuity caused featurally identical objects to be represented as different individuals. These results indicate that spatiotemporal continuity modulates neural representations of object identity, influencing judgments of object persistence even in the most staunchly "featural" areas of ventral visual cortex.     

Directed assembly of cell-laden microgels for fabrication of 3D tissue constructs

We present a bottom-up approach to direct the assembly of cell-laden microgels to generate tissue constructs with tunable microarchitecture and complexity. This assembly process is driven by the tendency of multiphase liquid-liquid systems to minimize the surface area and the resulting surface free energy between the phases. We demonstrate that shape-controlled microgels spontaneously assemble within multiphase reactor systems into predetermined geometric configurations. Furthermore, we characterize the parameters that influence the assembly process, such as external energy input, surface tension, and microgel dimensions. Finally, we show that multicomponent cell-laden constructs could be generated by assembling microgel building blocks and performing a secondary cross-linking reaction. This bottom-up approach for the directed assembly of cell-laden microgels provides a powerful and highly scalable approach to form biomimetic 3D tissue constructs and opens a paradigm for directing the assembly of mesoscale materials.     

Reputation for reciprocity engages the brain reward center

Brain reward circuitry, including ventral striatum and orbitofrontal cortex, has been independently implicated in preferences for fair and cooperative outcomes as well as learning of reputations. Using functional MRI (fMRI) and a “trust game” task involving iterative exchanges with fictive partners who acquire different reputations for reciprocity, we measured brain responses in 36 healthy adults when positive actions (entrust investment to partners) yield positive returns (reciprocity) and how these brain responses are modulated by partner reputation for repayment. Here we show that positive reciprocity robustly engages the ventral striatum and orbitofrontal cortex. Moreover, this signal of reciprocity in the ventral striatum appears selectively in response to partners who have consistently returned the investment (e.g., a reputation for reciprocity) and is absent for partners who lack a reputation for reciprocity. These findings elucidate a fundamental brain mechanism, via reward-related neural substrates, by which human cooperative relationships are initiated and sustained.     

Simple line drawings suffice for functional MRI decoding of natural scene categories

Humans are remarkably efficient at categorizing natural scenes. In fact, scene categories can be decoded from functional MRI (fMRI) data throughout the ventral visual cortex, including the primary visual cortex, the parahippocampal place area (PPA), and the retrosplenial cortex (RSC). Here we ask whether, and where, we can still decode scene category if we reduce the scenes to mere lines. We collected fMRI data while participants viewed photographs and line drawings of beaches, city streets, forests, highways, mountains, and offices. Despite the marked difference in scene statistics, we were able to decode scene category from fMRI data for line drawings just as well as from activity for color photographs, in primary visual cortex through PPA and RSC. Even more remarkably, in PPA and RSC, error patterns for decoding from line drawings were very similar to those from color photographs. These data suggest that, in these regions, the information used to distinguish scene category is similar for line drawings and photographs. To determine the relative contributions of local and global structure to the human ability to categorize scenes, we selectively removed long or short contours from the line drawings. In a category-matching task, participants performed significantly worse when long contours were removed than when short contours were removed. We conclude that global scene structure, which is preserved in line drawings, plays an integral part in representing scene categories.     

INAUGURAL ARTICLE by a Recently Elected Academy Member:Functional specificity in the human brain: A window into the functional architecture of the mind

Is the human mind/brain composed of a set of highly specialized components, each carrying out a specific aspect of human cognition, or is it more of a general-purpose device, in which each component participates in a wide variety of cognitive processes? For nearly two centuries, proponents of specialized organs or modules of the mind and brain—from the phrenologists to Broca to Chomsky and Fodor—have jousted with the proponents of distributed cognitive and neural processing—from Flourens to Lashley to McClelland and Rumelhart. I argue here that research using functional MRI is beginning to answer this long-standing question with new clarity and precision by indicating that at least a few specific aspects of cognition are implemented in brain regions that are highly specialized for that process alone. Cortical regions have been identified that are specialized not only for basic sensory and motor processes but also for the high-level perceptual analysis of faces, places, bodies, visually presented words, and even for the very abstract cognitive function of thinking about another person’s thoughts. I further consider the as-yet unanswered questions of how much of the mind and brain are made up of these functionally specialized components and how they arise developmentally.