Higher Cortical Areas Research Articles

Local organization of spatial and shape information in the primate prefrontal cortex.

The current understanding of sensory and motor cortical areas has been defined by the existence of topographical maps across the brain surface, however, higher cortical areas, such as the prefrontal cortex, seem to lack an equivalent organization, and only limited evidence of functional clustering of neurons with similar stimulus properties is evident in them. We thus sought to examine whether neurons that represent similar spatial and object information are clustered in the monkey prefrontal cortex and whether such an organization only emerges as a result of training. To this end, we analyzed neurophysiological recordings from male macaque monkeys before and after training in spatial and shape working memory tasks. Neurons with similar spatial or shape selectivity were more likely than chance to be encountered at short distances from each other. Some aspects of organization were present even in naïve animals, however other changes appeared after cognitive training. Our results reveal that prefrontal microstructure automatically supports orderly representations of spatial and object information.

Hue and orientation pinwheels in macaque area V4.

Area V4 is an intermediate-level area of the macaque visual cortical hierarchy that serves key functions in visual processing by integrating inputs from lower areas such as V1 and V2 and providing feedforward inputs to many higher cortical areas. Previous V4 imaging studies have focused on differential responses to color, orientation, disparity, and motion stimuli, but many details of the spatial organization of significant hue and orientation tuning have not been fully described. We used support vector machine (SVM) decoding of intrinsic cortical single-condition responses to generate high-resolution maps of hue and orientation tuning and to describe the organization of hue and orientation pinwheels in V4. Like V1 and V2, V4 contains maps of orientation that are organized as pinwheels. V4 also contains maps of hue that are organized as pinwheels, whose circular organization more closely represents the perception of hue than is observed in antecedent cortical areas. Unlike V1, where orientation is continuously mapped across the surface, V4 hue and orientation pinwheels are organized in limited numbers of pinwheel sequences. The organization of these sequences and the distance between pinwheels may provide insight into the functional organization of V4. Regions significantly tuned for hue occupy roughly four times that of the orientation, are largely separated from each other, and overlap by roughly 5%. This spatial organization is largely consistent with segregated inputs arising from V2 thin and interstripes. This modular organization of V4 suggests that further integration of color and shape might occur in higher areas in inferotemporal cortical.NEW & NOTEWORTHY The representation of hue and orientation in macaque monkey area V4 was determined by intrinsic cortical imaging of responses to isoluminant hues and achromatic grating stimuli. Vector summation of support vector machine (SVM) decoded single-condition responses was used to generate hue and orientation maps that, like V1 orientation maps, were both characterized by distinct pinwheel patterns. These data suggest that pinwheels are an important structure to represent different stimulus features across multiple visual cortical areas.

Mapping short association fibre connectivity up to V3 in the human brain in vivo.

Short association fibres (SAF) are the most abundant fibre pathways in the human white matter. Until recently, SAF could not be mapped comprehensively in vivo because diffusion weighted magnetic resonance imaging with sufficiently high spatial resolution needed to map these thin and short pathways was not possible. Recent developments in acquisition hardware and sequences allowed us to create a dedicated in vivo method for mapping the SAF based on sub-millimetre spatial resolution diffusion weighted tractography, which we validated in the human primary (V1) and secondary (V2) visual cortex against the expected SAF retinotopic order. Here, we extended our original study to assess the feasibility of the method to map SAF in higher cortical areas by including SAF up to V3. Our results reproduced the expected retinotopic order of SAF in the V2-V3 and V1-V3 stream, demonstrating greater robustness to the shorter V1-V2 and V2-V3 than the longer V1-V3 connections. The demonstrated ability of the method to map higher-order SAF connectivity patterns in vivo is an important step towards its application across the brain.

How Adversarial REM Dreams May Facilitate Creativity, and Why We Become Aware of Them

The importance of sleep for healthy brain function is widely acknowledged. However, it remains unclear how the internal generation of dreams might facilitate cognitive processes. In this perspective, we review a computational approach inspired by artificial intelligence that proposes a framework for how dreams occurring during rapid-eye-movement (REM) sleep can contribute to learning and creativity. In this framework, REM dreams are characterized by an adversarial process that, against the dream reality, tells a discriminator network to classify the internally created sensory activity as real. Such an adversarial dreaming process is shown to facilitate the emergence of real-world semantic representations in higher cortical areas. We further discuss the potential contributions of adversarial dreaming beyond learning, such as balancing fantastic and realistic dream elements and facilitating the occurrence of creative insights. We characterize non-REM (NREM) dreams, where a single hippocampal memory is replayed at a time, as serving the complementary role of improving the robustness of cortical representations to environmental perturbations. We finally explain how subjects can become aware of the adversarial REM dreams, but less of the NREM dreams, and how content- and state-awareness in wake, dream, and lucid dreaming may appear.

Metabolic and Skeletal Characterization of the KK/Ay Mouse Model-A Polygenic Mutation Model of Obese Type 2 Diabetes.

Type 2 diabetes (T2D) increases fracture incidence and fracture-related mortality rates (KK.Cg-Ay/J. The Jackson Laboratory; Available from: https://www.jax.org/strain/002468 ). While numerous mouse models for T2D exist, few effectively stimulate persistent hyperglycemia in both sexes, and even fewer are suitable for bone studies. Commonly used models like db/db and ob/ob have altered leptin pathways, confounding bone-related findings since leptin regulates bone properties (Fajardo et al. in Journal of Bone and Mineral Research 29(5): 1025-1040, 2014). The Yellow Kuo Kondo (KK/Ay) mouse, a polygenic mutation model of T2D, is able to produce a consistent diabetic state in both sexes and addresses the lack of a suitable model of T2D for bone studies. The diabetic state of KK/Ay stems from a mutation in the agouti gene, responsible for coat color in mice. This mutation induces ectopic gene expression across various tissue types, resulting in diabetic mice with yellow fur coats (Moussa and Claycombe in Obesity Research 7(5): 506-514, 1999). Male and female KK/Ay mice exhibited persistent hyperglycemia, defining them as diabetic with blood glucose (BG) levels consistently exceeding 300mg/dL. Notably, male control mice in this study were also diabetic, presenting a significant limitation. Nevertheless, male and female KK/Ay mice showed significantly elevated BG levels, HbA1c, and serum insulin concentration when compared to the non-diabetic female control mice. Early stages of T2D are characterized by hyperglycemia and hyperinsulinemia resulting from cellular insulin resistance, whereas later stages may feature hypoinsulinemia due to β-cell apoptosis (Banday et al. Avicenna Journal of Medicine 10(04): 174-188, 2020 and Klein et al. Cell Metabolism 34(1): 11-20, 2022). The observed hyperglycemia, hyperinsulinemia, and the absence of differences in β-cell mass suggest that KK/Ay mice in this studyare modeling the earlier stages of T2D. While compromised bone microarchitecture was observed in this study, older KK/Ay mice, representing more advanced stages of T2D, might exhibit more pronounced skeletal manifestations. Compared to the control group, the femora of KK/Ay mice had higher cortical area and cortical thickness, and improved trabecular properties which would typically be indicative of greater bone strength. However, KK/Ay mice displayed lower cortical tissue mineral density in both sexes and increased cortical porosity in females. Fracture instability toughness of the femora was lower in KK/Ay mice overall compared to controls. These findings indicate that decreased mechanical integrity noted in the femora of KK/Ay mice was likely due to overall bone quality being compromised.

Modular horizontal network within mouse primary visual cortex.

Interactions between feedback connections from higher cortical areas and local horizontal connections within primary visual cortex (V1) were shown to play a role in contextual processing in different behavioral states. Layer 1 (L1) is an important part of the underlying network. This cell-sparse layer is a target of feedback and local inputs, and nexus for contacts onto apical dendrites of projection neurons in the layers below. Importantly, L1 is a site for coupling inputs from the outside world with internal information. To determine whether all of these circuit elements overlap in L1, we labeled the horizontal network within mouse V1 with anterograde and retrograde viral tracers. We found two types of local horizontal connections: short ones that were tangentially limited to the representation of the point image, and long ones which reached beyond the receptive field center, deep into its surround. The long connections were patchy and terminated preferentially in M2 muscarinic acetylcholine receptor-negative (M2-) interpatches. Anterogradely labeled inputs overlapped in M2-interpatches with apical dendrites of retrogradely labeled L2/3 and L5 cells, forming module-selective loops between topographically distant locations. Previous work showed that L1 of M2-interpatches receive inputs from the lateral posterior thalamic nucleus (LP) and from a feedback network from areas of the medial dorsal stream, including the secondary motor cortex. Together, these findings suggest that interactions in M2-interpatches play a role in processing visual inputs produced by object-and self-motion.

Experimental evidence for involvement of monocular channels in mental rotation.

According to the prevailing view, cognitive processes of mental rotation are carried out by visuospatial perceptual circuits located primarily in high cortical areas. Here, we examined the functional involvement of (mostly subcortical) monocular channels in mental rotation tasks. Images of two rotated objects (0°, 50°, 100°, or 150°; identical or mirrored) were presented either to one eye (monocular) or segregated between the eyes (interocular). The results indicated a causal role for low monocular visual channels in mental rotation: Response times for identical ("same") objects at high angular disparities (100°, 150°) were shorter when both objects were presented to a single eye than when each object was presented to a different eye. We suggest that mental rotation processes rely on cortico-subcortical loops that support visuospatial perception. More generally, the findings highlight the potential contribution of lower-level mechanisms to what are typically considered to be high-level cognitive functions, such as mental representation.

Object Relations: How Early Relationships Create Map for Later Ones

Object Relations: How Early Relationships Create Map for Later Ones

Lower limb bone structure of Middle Pleistocene hominins from the Caune de l’Arago (Tautavel, France): Evolutionary and functional comparison with the penecontemporaneous hominins of Sima de los Huesos (Atapuerca, Spain)

The Caune de l’Arago (Arago) and Sima de los Huesos (Sima) human bones from the European Middle Pleistocene are penecontemporaneous, although the Sima hominins are closely related to Neandertal, and Arago hominins present more archaic features. In previous and in press studies, the cross-sectional geometric properties (CSG) of lower limb bones of Arago and Sima have been studied separately without comparative analyses. Here, in order to bridge this gap, we use the same criteria for both samples to highlight evolutionary affinities and to compare their level and pattern of mobility. This study focuses on the femur, fibula and tibia from Arago and Sima with references to fossils from the sites of Trinil, Zhoukoudian and Lazaret, and ancient and recent Homo sapiens (including athletes and non-athletes). We analyze the cross-sectional areas, biomechanical bone “shape” indices (Ix/Iy, Imax/Imin) and pattern of cortical bone distribution. All lower limb bones from Arago have noticeably high to very high relative cortical areas and low to very low medullary areas. The overall femoral pattern in Arago, like Sima, is similar to that of Middle Pleistocene hominins (e.g., low femoral shape indices, Ix/Iy) and Neandertals (e.g., large cross-sectional size). However, the femoral midshaft in Sima presents prominent posteromedial cortical thickening, as a result of a spiral cortical reinforcement along the medial side of the diaphysis. This characteristic is specific to Neandertal and some Middle Pleistocene hominins. In contrast, the midshaft femoral pattern in Arago is close to that of some Homo erectus. We also note that the femoral cross-sectional size and relative cortical area in Arago differ drastically to the small size and low relative cortical area of Lazaret and Trinil hominins. The very high shape index at midshaft (i.e., high Imax/Imin) of the Arago tibia is observed in ancient H. sapiens and runners; the tibial posterior “pilaster” is found in Neandertals and ancient H. sapiens; and the flat or convex tibial faces are similar to Neandertals. Furthermore, the Arago fibulas show marked fibular posterolateral cortical reinforcement with low anteroposterior strengthening. These leg features (tibia, fibula) are also found in some Sima hominins (but not in all individuals). Consequently, this study confirms the presence of archaic features in Arago and the close evolutionary relationship between Sima and Neandertal. This proposition is mainly based on the femoral midshaft pattern influenced by the pelvofemoral complex, considered to be substantially genetically controlled. The leg functional analysis highlights a high level of mobility and travelling in uneven terrains or in mountainous areas in Arago, consistent with known environments and hunting practices. Previously, an analogous hypothesis was proposed put forward for Sima hominins.

Horizontal connectivity in V1: Prediction of coherence in contour and motion integration

This study demonstrates the functional importance of the Surround context relayed laterally in V1 by the horizontal connectivity, in controlling the latency and the gain of the cortical response to the feedforward visual drive. We report here four main findings: 1) a centripetal apparent motion sequence results in a shortening of the spiking latency of V1 cells, when the orientation of the local inducer and the global motion axis are both co-aligned with the RF orientation preference; 2) this contextual effects grows with visual flow speed, peaking at 150–250°/s when it matches the propagation speed of horizontal connectivity (0.15–0.25 mm/ms); 3) For this speed range, the axial sensitivity of V1 cells is tilted by 90° to become co-aligned with the orientation preference axis; 4) the strength of modulation by the surround context correlates with the spatiotemporal coherence of the apparent motion flow. Our results suggest an internally-generated binding process, linking local (orientation /position) and global (motion/direction) features as early as V1. This long-range diffusion process constitutes a plausible substrate in V1 of the human psychophysical bias in speed estimation for collinear motion. Since it is demonstrated in the anesthetized cat, this novel form of contextual control of the cortical gain and phase is a built-in property in V1, whose expression does not require behavioral attention and top-down control from higher cortical areas. We propose that horizontal connectivity participates in the propagation of an internal “prediction” wave, shaped by visual experience, which links contour co-alignment and global axial motion at an apparent speed in the range of saccade-like eye movements.

Serum 25-Hydroxyvitamin D is Associated With Bone Microarchitecture and Strength in a Multiracial Cohort of Young Adults.

To determine whether 25-hydroxyvitamin D (25-OH D) levels are associated with bone outcomes in a multiracial cohort of young adults. This cross-sectional study included 165 participants (83 men, 82 women, 18-30 years of age) who self-identified as Asian, Black, or White. We measured bone microarchitecture and strength of the distal radius and tibia using high-resolution peripheral quantitative computed tomography. We used linear regression to estimate the association between 25-OH D (ng/mL) and bone measurements, adjusting for race, sex, age, weight, height, calcium intake, physical activity, and season. A total of 43.6% of participants were 25-OH D deficient (<20 ng/mL) with greater prevalence in Asian (38.9%) and Black (43.1%) compared with White (18.0%) participants (P < 0.001). At the distal radius, 25-OH D was positively associated with cortical area, trabecular density, cortical thickness, cortical porosity, and failure load (P < 0.05 for all). At the distal tibia, higher 25-OH D was associated with higher cortical area, trabecular density, trabecular number, failure load, and lower trabecular separation and cortical density (P < 0.05 for all). After multivariable adjustment, those with 25-OH D deficiency had generally worse bone microarchitecture than those with 25-OH D sufficiency. Black individuals had largely more favorable bone outcomes than Asian and White individuals, despite higher prevalence of 25-OH D deficiency. We found a high prevalence of 25-OH D deficiency in a multiracial cohort of young adults. Lower 25-OH D was associated with worse bone outcomes at the distal radius and tibia at the time of peak bone mass, warranting further attention to vitamin D status in young adults.

High-Density Electroencephalography-Informed Multiband Functional Magnetic Resonance Imaging Reveals Rhythm-Specific Activations Within the Trigeminal Nociceptive Network.

The interest in exploring trigeminal pain processing has grown in recent years, mainly due to various pathologies (such as migraine) related to this system. However, research efforts have mainly focused on understanding molecular mechanisms or studying pathological states. On the contrary, non-invasive imaging studies are limited by either spatial or temporal resolution depending on the modality used. This can be overcome by using multimodal imaging techniques such as simultaneous functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). Although this technique has already been applied to neuroscientific research areas and consequently gained insights into diverse sensory systems and pathologies, only a few studies have applied EEG-fMRI in the field of pain processing and none in the trigeminal system. Focusing on trigeminal nociception, we used a trigeminal pain paradigm, which has been well-studied in either modality. For validation, we first acquired stand-alone measures with each imaging modality before fusing them in a simultaneous session. Furthermore, we introduced a new, yet simple, non-parametric correlation technique, which exploits trial-to-trial variance of both measurement techniques with Spearman’s correlations, to consolidate the results gained by the two modalities. This new technique does not presume a linear relationship and needs a few repetitions per subject. We also showed cross-validation by analyzing visual stimulations. Using these techniques, we showed that EEG power changes in the theta-band induced by trigeminal pain correlate with fMRI activation within the brainstem, whereas those of gamma-band oscillations correlate with BOLD signals in higher cortical areas.

Feedforward and feedback interactions between visual cortical areas use different population activity patterns

Brain function relies on the coordination of activity across multiple, recurrently connected brain areas. For instance, sensory information encoded in early sensory areas is relayed to, and further processed by, higher cortical areas and then fed back. However, the way in which feedforward and feedback signaling interact with one another is incompletely understood. Here we investigate this question by leveraging simultaneous neuronal population recordings in early and midlevel visual areas (V1–V2 and V1–V4). Using a dimensionality reduction approach, we find that population interactions are feedforward-dominated shortly after stimulus onset and feedback-dominated during spontaneous activity. The population activity patterns most correlated across areas were distinct during feedforward- and feedback-dominated periods. These results suggest that feedforward and feedback signaling rely on separate “channels”, which allows feedback signals to not directly affect activity that is fed forward.

Hearing Loss Increases Inhibitory Effects of Prefrontal Cortex Stimulation on Sound Evoked Activity in Medial Geniculate Nucleus.

Sensory gating is the process whereby irrelevant sensory stimuli are inhibited on their way to higher cortical areas, allowing for focus on salient information. Sensory gating circuitry includes the thalamus as well as several cortical regions including the prefrontal cortex (PFC). Defective sensory gating has been implicated in a range of neurological disorders, including tinnitus, a phantom auditory perception strongly associated with cochlear trauma. Recently, we have shown in rats that functional connectivity between PFC and auditory thalamus, i.e., the medial geniculate nucleus (MGN), changes following cochlear trauma, showing an increased inhibitory effect from PFC activation on the spontaneous firing rate of MGN neurons. In this study, we further investigated this phenomenon using a guinea pig model, in order to demonstrate the validity of our finding beyond a single species and extend data to include data on sound evoked responses. Effects of PFC electrical stimulation on spontaneous and sound-evoked activity of single neurons in MGN were recorded in anaesthetised guinea pigs with normal hearing or hearing loss 2 weeks after acoustic trauma. No effect, inhibition and excitation were observed following PFC stimulation. The proportions of these effects were not different in animals with normal hearing and hearing loss but the magnitude of effect was. Indeed, hearing loss significantly increased the magnitude of inhibition for sound evoked responses, but not for spontaneous activity. The findings support previous observations that PFC can modulate MGN activity and that functional changes occur within this pathway after cochlear trauma. These data suggest hearing loss can alter sensory gating which may be a contributing factor toward tinnitus development.

Ipsilateral Stimulus Encoding in Primary and Secondary Somatosensory Cortex of Awake Mice.

Lateralization is a hallmark of somatosensory processing in the mammalian brain. However, in addition to their contralateral representation, unilateral tactile stimuli also modulate neuronal activity in somatosensory cortices of the ipsilateral hemisphere. The cellular organization and functional role of these ipsilateral stimulus responses in awake somatosensory cortices, especially regarding stimulus coding, are unknown. Here, we targeted silicon probe recordings to the vibrissa region of primary (S1) and secondary (S2) somatosensory cortex of awake head-fixed mice of either sex while delivering ipsilateral and contralateral whisker stimuli. Ipsilateral stimuli drove larger and more reliable responses in S2 than in S1, and activated a larger fraction of stimulus-responsive neurons. Ipsilateral stimulus-responsive neurons were rare in layer 4 of S1, but were located in equal proportion across all layers in S2. Linear classifier analyses further revealed that decoding of the ipsilateral stimulus was more accurate in S2 than S1, whereas S1 decoded contralateral stimuli most accurately. These results reveal substantial encoding of ipsilateral stimuli in S1 and especially S2, consistent with the hypothesis that higher cortical areas may integrate tactile inputs across larger portions of space, spanning both sides of the body.SIGNIFICANCE STATEMENT Tactile information obtained by one side of the body is represented in the activity of neurons of the opposite brain hemisphere. However, unilateral tactile stimulation also modulates neuronal activity in the other, or ipsilateral, brain hemisphere. This ipsilateral activity may play an important role in the representation and processing of tactile information, in particular when the sense of touch involves both sides of the body. Our work in the whisker system of awake mice reveals that neocortical ipsilateral activity, in particular that of deep layer excitatory neurons of secondary somatosensory cortex (S2), contains information about the presence and the velocity of unilateral tactile stimuli, which supports a key role for S2 in integrating tactile information across both body sides.

Corticothalamic Projections Gate Alpha Rhythms in the Pulvinar.

Two types of corticothalamic (CT) terminals reach the pulvinar nucleus of the thalamus, and their distribution varies according to the hierarchical level of the cortical area they originate from. While type 2 terminals are more abundant at lower hierarchical levels, terminals from higher cortical areas mostly exhibit type 1 axons. Such terminals also evoke different excitatory postsynaptic potential dynamic profiles, presenting facilitation for type 1 and depression for type 2. As the pulvinar is involved in the oscillatory regulation between intercortical areas, fundamental questions about the role of these different terminal types in the neuronal communication throughout the cortical hierarchy are yielded. Our theoretical results support that the co-action of the two types of terminals produces different oscillatory rhythms in pulvinar neurons. More precisely, terminal types 1 and 2 produce alpha-band oscillations at a specific range of connectivity weights. Such oscillatory activity is generated by an unstable transition of the balanced state network’s properties that it is found between the quiescent state and the stable asynchronous spike response state. While CT projections from areas 17 and 21a are arranged in the model as the empirical proportion of terminal types 1 and 2, the actions of these two cortical connections are antagonistic. As area 17 generates low-band oscillatory activity, cortical area 21a shifts pulvinar responses to stable asynchronous spiking activity and vice versa when area 17 produces an asynchronous state. To further investigate such oscillatory effects through corticothalamo-cortical projections, the transthalamic pathway, we created a cortical feedforward network of two cortical areas, 17 and 21a, with CT connections to a pulvinar-like network with two cortico-recipient compartments. With this model, the transthalamic pathway propagates alpha waves from the pulvinar to area 21a. This oscillatory transfer ceases when reciprocal connections from area 21a reach the pulvinar, closing the CT loop. Taken together, results of our model suggest that the pulvinar shows a bi-stable spiking activity, oscillatory or regular asynchronous spiking, whose responses are gated by the different activation of cortico-pulvinar projections from lower to higher-order areas such as areas 17 and 21a.

Visual exposure enhances stimulus encoding and persistence in primary cortex

The brain adapts to the sensory environment. For example, simple sensory exposure can modify the response properties of early sensory neurons. How these changes affect the overall encoding and maintenance of stimulus information across neuronal populations remains unclear. We perform parallel recordings in the primary visual cortex of anesthetized cats and find that brief, repetitive exposure to structured visual stimuli enhances stimulus encoding by decreasing the selectivity and increasing the range of the neuronal responses that persist after stimulus presentation. Low-dimensional projection methods and simple classifiers demonstrate that visual exposure increases the segregation of persistent neuronal population responses into stimulus-specific clusters. These observed refinements preserve the representational details required for stimulus reconstruction and are detectable in postexposure spontaneous activity. Assuming response facilitation and recurrent network interactions as the core mechanisms underlying stimulus persistence, we show that the exposure-driven segregation of stimulus responses can arise through strictly local plasticity mechanisms, also in the absence of firing rate changes. Our findings provide evidence for the existence of an automatic, unguided optimization process that enhances the encoding power of neuronal populations in early visual cortex, thus potentially benefiting simple readouts at higher stages of visual processing.

Higher Serum 25-Hydroxy Vitamin D Is Associated With Better Measures of Bone Microarchitecture and Strength

ObjectivesTo determine whether serum 25-hydroxy vitamin D (25-OH D) levels are associated with bone microarchitecture and strength in a multi-racial cohort of young adults. We also determined if race and calcium intake modified these associations. MethodsThis cross-sectional study included 176 young adults who identified as Asian, Black, or White (50% women). High-resolution peripheral quantitative computed tomography (HR-pQCT, 2nd generation) scans of the distal radius and tibia were used to assess bone microarchitecture and strength by micro-finite element analysis. We measured 25-OH D levels (ng/mL, immunoassay), dietary intake (Block’s Food Frequency Questionnaire), and physical activity (questionnaire). We used linear regression to estimate the association between 25-OH D and standardized bone measures, adjusting for race, sex, age, weight, height, calcium intake, and physical activity. The interactions of 25-OH D with race and calcium intake (mg/d) were tested and models were stratified for significant interactions (P < 0.05). ResultsMean age and BMI were 23.7 ± 3.1 years and 24.1 ± 3.1 kg/m2, respectively. 43.9% of the subjects were vitamin D deficient (<20 ng/ml) with greater prevalence in Asian (38.9%) and Black (43.1%) compared to White (18.1%) subjects (P < 0.001 for group differences). At the distal radius, higher 25-OH D was related with higher cortical area (β ± SE = 0.018 ± 0.006, P = 0.005), cortical porosity (β ± SE = 0.023 ± 0.008, P = 0.006) and failure load (β ± SE = 0.023 ± 0.007, P = 0.001). At the distal tibia, higher 25-OH D was related with higher trabecular density (β ± SE = 0.020 ± 0.008, P = 0.015), trabecular thickness (β = 0.016 ± 0.008 P = 0.044) and lower trabecular separation (β ± SE = –0.017 ± 0.008 P = 0.046). There were no significant interactions for 25-OH D and calcium intake. Significant interactions were seen for 25-OH D and race, with stronger associations observed in White compared to Asian or Black subjects. ConclusionsThis study suggests that higher 25-OH D is associated with better bone microarchitecture and strength at the distal radius and tibia in young adults. As poor bone microarchitecture is associated with increased fracture risk, these findings may have implications for fracture risk later in life. Funding SourcesU.S. Army Medical Research Acquisition Activity.

Decoding Concurrent Representations of Pitch and Location in Auditory Working Memory.

Multivariate analyses of hemodynamic signals serve to identify the storage of specific stimulus contents in working memory (WM). Representations of visual stimuli have been demonstrated both in sensory regions and in higher cortical areas. While previous research has typically focused on the WM maintenance of a single content feature, it remains unclear whether two separate features of a single object can be decoded concurrently. Also, much less evidence exists for representations of auditory compared with visual stimulus features. To address these issues, human participants had to memorize both pitch and perceived location of one of two sample sounds. After a delay phase, they were asked to reproduce either pitch or location. At recall, both features showed comparable levels of discriminability. Region of interest (ROI)-based decoding of functional magnetic resonance imaging (fMRI) data during the delay phase revealed feature-selective activity for both pitch and location of a memorized sound in auditory cortex and superior parietal lobule. The latter region showed higher decoding accuracy for location than pitch. In addition, location could be decoded from angular and supramarginal gyrus and both superior and inferior frontal gyrus. The latter region also showed a trend for decoding of pitch. We found no region exclusively coding pitch memory information. In summary, the present study yielded evidence for concurrent representations of pitch and location of a single object both in sensory cortex and in hierarchically higher regions, pointing toward representation formats that enable feature integration within the same anatomic brain regions.SIGNIFICANCE STATEMENT Decoding of hemodynamic signals serves to identify brain regions involved in the storage of stimulus-specific information in working memory (WM). While to-be-remembered information typically consists of several features, most previous investigations have focused on the maintenance of one memorized feature belonging to one visual object. The present study assessed the concurrent storage of two features of the same object in auditory WM. We found that both pitch and location of memorized sounds were decodable both in early sensory areas, in higher-level superior parietal cortex and, to a lesser extent, in inferior frontal cortex. While auditory cortex is known to process different features in parallel, their concurrent representation in parietal regions may support the integration of object features in WM.

Cortical ensembles selective for context

Neural processing of sensory information is strongly influenced by context. For instance, cortical responses are reduced to predictable stimuli, while responses are increased to novel stimuli that deviate from contextual regularities. Such bidirectional modulation based on preceding sensory context is likely a critical component or manifestation of attention, learning, and behavior, yet how it arises in cortical circuits remains unclear. Using volumetric two-photon calcium imaging and local field potentials in primary visual cortex (V1) from awake mice presented with visual "oddball" paradigms, we identify both reductions and augmentations of stimulus-evoked responses depending, on whether the stimulus was redundant or deviant, respectively. Interestingly, deviance-augmented responses were limited to a specific subset of neurons mostly in supragranular layers. These deviance-detecting cells were spatially intermixed with other visually responsive neurons and were functionally correlated, forming a neuronal ensemble. Optogenetic suppression of prefrontal inputs to V1 reduced the contextual selectivity of deviance-detecting ensembles, demonstrating a causal role for top-down inputs. The presence of specialized context-selective ensembles in primary sensory cortex, modulated by higher cortical areas, provides a circuit substrate for the brain's construction and selection of prediction errors, computations which are key for survival and deficient in many psychiatric disorders.