Distinct Subregions Research Articles

Medial Temporal Lobe Networks in Alzheimer's Disease: Structural and Molecular Vulnerabilities.

The medial temporal lobe (MTL) is connected to the rest of the brain through two main networks: the anterior-temporal (AT) and the posterior-medial (PM) systems. Given the crucial role of the MTL and networks in the physiopathology of Alzheimer's disease (AD), the present study aimed at (1) investigating whether MTL atrophy propagates specifically within the AT and PM networks, and (2) evaluating the vulnerability of these networks to AD proteinopathies. To do that, we used neuroimaging data acquired in human male and female in three distinct cohorts: (1) resting-state functional MRI (rs-fMRI) from the aging brain cohort (ABC) to define the AT and PM networks (n = 68); (2) longitudinal structural MRI from Alzheimer's disease neuroimaging initiative (ADNI)GO/2 to highlight structural covariance patterns (n = 349); and (3) positron emission tomography (PET) data from ADNI3 to evaluate the networks' vulnerability to amyloid and tau (n = 186). Our results suggest that the atrophy of distinct MTL subregions propagates within the AT and PM networks in a dissociable manner. Brodmann area (BA)35 structurally covaried within the AT network while the parahippocampal cortex (PHC) covaried within the PM network. In addition, these networks are differentially associated with relative tau and amyloid burden, with higher tau levels in AT than in PM and higher amyloid levels in PM than in AT. Our results also suggest differences in the relative burden of tau species. The current results provide further support for the notion that two distinct MTL networks display differential alterations in the context of AD. These findings have important implications for disease spread and the cognitive manifestations of AD.SIGNIFICANCE STATEMENT The current study provides further support for the notion that two distinct medial temporal lobe (MTL) networks, i.e., anterior-temporal (AT) and the posterior-medial (PM), display differential alterations in the context of Alzheimer's disease (AD). Importantly, neurodegeneration appears to occur within these networks in a dissociable manner marked by their covariance patterns. In addition, the AT and PM networks are also differentially associated with relative tau and amyloid burden, and perhaps differences in the relative burden of tau species [e.g., neurofibriliary tangles (NFTs) vs tau in neuritic plaques]. These findings, in the context of a growing literature consistent with the present results, have important implications for disease spread and the cognitive manifestations of AD in light of the differential cognitive processes ascribed to them.

Multi-year assessment of immature bull shark Carcharhinus leucas residency and activity spaces in an expansive estuarine nursery

Although portions of the Indian River Lagoon (IRL), Florida (USA), serve as essential fish habitat for US Atlantic coast bull sharks Carcharhinus leucas, past studies were short-term (days to months) and encompassed only small parts of this expansive estuarine system. In this study, 29 immature bull sharks were tracked in the IRL between Port St. John and Port Salerno, Florida, and in adjacent shelf waters for up to 4 yr using passive acoustic telemetry. Dynamic Brownian bridge movement models showed small daily (50% utilization distribution [UD] = 1.00 km2, 95% UD = 4.36 km2) and monthly (50% UD = 4.88 km2, 95% UD = 24.67 km2) mean activity spaces that seasonally shifted (October-March) to include adjacent coastal waters. Tracked bull sharks were found to display residency in the IRL and in distinct subregions of the system. Analysis confirmed that bull shark nursery habitat extends south of Sebastian Inlet to Port Salerno, approximately 86 km farther south than previously described, and that adjacent shelf waters, which had not been studied, are important to immature bull sharks during cooler months. This study provides the first multi-year assessment of bull shark space use in the IRL, with improved resolution and over a greater expanse of the system than past studies. These movement data will be important to understanding how young bull sharks may be affected by anthropogenic stressors in this highly impacted lagoonal estuary.

Altered dynamic functional connectivity of insular subregions could predict symptom severity of male patients with autism spectrum disorder

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by difficulties with social communication and restricted or repetitive patterns of behavior. This disorder was characterized by widespread abnormalities involving distributed brain networks. As one such key network node, the insular cortex has been regarded as a research focus of ASD neuropathology. The insula is a functionally complex brain structure. However, it is not fully clear if dynamic characteristics of resting-state functional magnetic resonance imaging (R-fMRI) signals in insular heterogeneous could be used to depict abnormalities in ASD. To address this question, we investigated dynamic functional connectivity (dFC) of 12 insular subregions. Data were obtained from 44 individuals with ASD and 65 typically developing age-matched controls (TDC). We assessed dFC by sliding-window method and quantified its temporal variability. Multivariable linear regression models were constructed to determine whether dFC support complementary information about symptom severity of individuals with ASD rather than static functional connectivity (sFC). The results showed that individuals with ASD exhibited dFC and sFC alterations in distinct insular subregions. Some brain regions showed only abnormal dFC but not sFC with insular subregions. These abnormal dFC could significantly predict the symptom severity of individuals with ASD. Our findings might advance our knowledge about the potential of insular heterogeneity and dynamic characteristics in understanding the neuropathology mechanism of ASD and in developing neuroimaging biomarkers for clinical applications.

Functional Subdivisions of the Cerebellum in Naturalistic Paradigm Functional Magnetic Resonance Imaging.

Compelling evidence has suggested that the human cerebellum is engaged in a wide range of cognitive tasks besides traditional opinions of motor control, and it is organized into a set of distinct functional subregions. The existing model-driven cerebellum parcellations through resting-state functional MRI (rsfMRI) and task-fMRI are relatively coarse, introducing challenges in resolving the functions of the cerebellum especially when the brain is exposed to naturalistic environments. The current study took the advantages of the naturalistic paradigm (i.e., movie viewing) fMRI (nfMRI) to derive fine parcellations via a data-driven dual-regression-like sparse representation framework. The parcellations were quantitatively evaluated by functional homogeneity, and global and local boundary confidence. In addition, the differences of cerebellum–cerebrum functional connectivities between rsfMRI and nfMRI for some exemplar parcellations were compared to provide qualitatively functional validations. Our experimental results demonstrated that the proposed study successfully identified distinct subregions of the cerebellum. This fine parcellation may serve as a complementary solution to existing cerebellum parcellations, providing an alternative template for exploring neural activities of the cerebellum in naturalistic environments.

Immunolabeling Provides Evidence for Subregions in the Songbird Nucleus Accumbens and Suggests a Context-Dependent Role in Song in Male European Starlings (Sturnus vulgaris)

Birdsong is well known for its role in mate attraction during the breeding season. However, many birds, including European starlings (Sturnus vulgaris), also sing outside the breeding season as part of large flocks. Song in a breeding context can be extrinsically rewarded by mate attraction; however, song in nonbreeding flocks, referred to here as gregarious song, results in no obvious extrinsic reward and is proposed to be intrinsically rewarded. The nucleus accumbens (NAC) is a brain region well known to mediate reward and motivation, which suggests it is an ideal candidate to regulate reward associated with gregarious song. The goal of this study was to provide new histochemical information on the songbird NAC and its subregions (rostral pole, core, and shell) and to begin to determine subregion-specific contributions to gregarious song in male starlings. We examined immunolabeling for tyrosine hydroxylase (TH), neurotensin, and enkephalin (ENK) in the NAC. We then examined the extent to which gregarious and sexually motivated song differentially correlated with immunolabeling for the immediate early genes FOS and ZENK in each subdivision of the NAC. We found that TH and ENK labeling within subregions of the starling NAC was generally similar to patterns seen in the core and shell of NACs in mammals and birds. Additionally, we found that gregarious song, but not sexually motivated song, positively correlated with FOS in all NAC subregions. Our observations provide further evidence for distinct subregions within the songbird NAC and suggest the NAC may play an important role in regulating gregarious song in songbirds.

Mapping the magnetic field in the Taurus/B211 filamentary cloud with SOFIA HAWC + and comparing with simulation

ABSTRACT Optical and infrared polarization mapping and recent Planck observations of the filametary cloud L1495 in Taurus show that the large-scale magnetic field is approximately perpendicular to the long axis of the cloud. We use the HAWC + polarimeter on SOFIA to probe the complex magnetic field in the B211 part of the cloud. Our results reveal a dispersion of polarization angles of 36°, about five times that measured on a larger scale by Planck. Applying the Davis–Chandrasekhar–Fermi (DCF) method with velocity information obtained from Institut de Radioastronomie Millimétrique 30 m C18O(1-0) observations, we find two distinct sub-regions with magnetic field strengths differing by more than a factor 3. The quieter sub-region is magnetically critical and sub-Alfv$\acute{\rm e}$nic; the field is comparable to the average field measured in molecular clumps based on Zeeman observations. The more chaotic, super-Alfv$\acute{\rm e}$nic sub-region shows at least three velocity components, indicating interaction among multiple substructures. Its field is much less than the average Zeeman field in molecular clumps, suggesting that the DCF value of the field there may be an underestimate. Numerical simulation of filamentary cloud formation shows that filamentary substructures can strongly perturb the magnetic field. DCF and true field values in the simulation are compared. Pre-stellar cores are observed in B211 and are seen in our simulation. The appendices give a derivation of the standard DCF method that allows for a dispersion in polarization angles that is not small, present an alternate derivation of the structure function version of the DCF method, and treat fragmentation of filaments.

High-Resolution, 3D Imaging of the Zebrafish Gill-Associated Lymphoid Tissue (GIALT) Reveals a Novel Lymphoid Structure, the Amphibranchial Lymphoid Tissue.

The zebrafish is extensively used as an animal model for human and fish diseases. However, our understanding of the structural organization of its immune system remains incomplete, especially the mucosa-associated lymphoid tissues (MALTs). Teleost MALTs are commonly perceived as diffuse and scattered populations of immune cells throughout the mucosa. Yet, structured MALTs have been recently discovered in Atlantic salmon (Salmo salar L.), including the interbranchial lymphoid tissue (ILT) in the gills. The existence of the ILT was only recently identified in zebrafish and other fish species, highlighting the need for in-depth characterizations of the gill-associated lymphoid tissue (GIALT) in teleosts. Here, using 3-D high-resolution microscopy, we analyze the GIALT of adult zebrafish with an immuno-histology approach that reveals the organization of lymphoid tissues via the labeling of T/NK cells with an antibody directed to a highly conserved epitope on the kinase ZAP70. We show that the GIALT in zebrafish is distributed over at least five distinct sub-regions, an organization found in all pairs of gill arches. The GIALT is diffuse in the pharyngeal part of the gill arch, the interbranchial septum and the filaments/lamellae, and structured in two sub-regions: the ILT, and a newly discovered lymphoid structure located along each side of the gill arch, which we named the Amphibranchial Lymphoid Tissue (ALT). Based on RAG2 expression, neither the ILT nor the ALT constitute additional thymi. The ALT shares several features with the ILT such as presence of abundant lymphoid cells and myeloid cells embedded in a network of reticulated epithelial cells. Further, the ILT and the ALT are also a site for T/NK cell proliferation. Both ILT and ALT show structural changes after infection with Spring Viraemia of Carp Virus (SVCV). Together, these data suggest that ALT and ILT play an active role in immune responses. Comparative studies show that whereas the ILT seems absent in most neoteleosts (“Percomorphs”), the ALT is widely present in cyprinids, salmonids and neoteleosts, suggesting that it constitutes a conserved tissue involved in the protection of teleosts via the gills.

NIMG-55. AUGMENTED INTELLIGENCE IS SUPERIOR TO ARTIFICIAL INTELLIGENCE! HUMAN-COMPUTER SYNERGY FOR GENERATING HIGH QUALITY GLIOBLASTOMA SUB-REGION SEGMENTATIONS

Abstract PURPOSE Artificial intelligence (AI) is poised to improve diagnostic methods in neuro-oncologic imaging and contribute to patient management by analyzing pre-operative MRI scans. AI results are better interpreted by compartmentalizing glioblastoma into distinct sub-regions, i.e., necrotic core, enhancing tumor, peritumoral T2/FLAIR signal abnormality (ED). Manual delineation of these sub-regions by expert neuroradiologists is impractical, requiring hours for intricate cases. Computer-aided segmentation (CAS) can mitigate this issue but is limited in the quality of the produced segmentations. We hypothesize that CAS followed by expert refinements is more practical/time-efficient. METHODS CAS was used on a total of 359 glioblastoma patients with four MRI sequences (T1, T1Gd, T2, T2-FLAIR) from each patient. All segmentations were sent to expert neuroradiologist annotators for manual refinements. Once refined, our team including two senior attending neuroradiologists with ≥13 years of experience each, reviewed and either approved or returned the segmentations to individual annotators for further refinements. Total time required to refine and review the finalized segmentations was measured. RESULTS Following one round of refinements by expert annotators, 244/359 (68%) segmentations were approved by our team while 115/359 (32%) segmentations contained a variety of errors that required a second round of refinements. The most common observed errors were 1) missed ED in the anterior/inferior temporal lobes and corpus callosum (37/115 cases, 32%) and 2) erroneous segmentation of normal choroid plexus and blood vessels (14/115 cases, 12%). The expert annotators required 120 hours to refine all 359 segmentations, and our team required 26 additional hours to review them, resulting in 24 minutes/segmentation following CAS. CONCLUSION Our findings support the value of a well-communicated annotation protocol to coordinate CAS and expert annotators. With CAS, our team and expert annotators rapidly finalized segmentations for 359 glioblastoma patients, demonstrating the value of a synergistic approach to creating high quality tumor sub-region segmentations.

Attentional bias to threat and gray matter volume morphology in high anxious individuals.

In a sample of highly anxious individuals, the relationship between gray matter volume brain morphology and attentional bias to threat was assessed. Participants performed a dot-probe task of attentional bias to threat and gray matter volume was acquired from whole brain structural T1-weighted magnetic resonance imaging scans. The results replicate previous findings in unselected samples that elevated attentional bias to threat is linked to greater gray matter volume in the middle frontal gyrus and superior frontal gyrus. In addition, we provide novel evidence that elevated attentional bias to threat is associated with greater gray matter volume in the inferior frontal gyrus, insula, cerebellum, and other distributed regions. Lastly, exploratory analyses provide initial evidence that distinct subregions of the right posterior parietal cortex may contribute to attentional bias in a sex-specific manner. Our results illuminate how differences in gray matter volume morphology relate to attentional bias to threat in anxious individuals. This knowledge could inform neurocognitive models of anxiety-related attentional bias to threat.

Assessing the Role of Snow Cover for Post‐Wildfire Revegetation Across the Pacific Northwest

AbstractForested, mountain landscapes in the Pacific Northwest (PNW) are changing at an unprecedented rate, largely due to shifts in the regional climate regime. Documented climate warming trends across the PNW include increasing wildfire frequency and severity and an increasingly ephemeral snowpack, especially at moderate elevations. We analyzed 24 high severity wildfires across four distinct PNW mountainous subregions, examining snow‐vegetation relationships for two years pre‐fire and four years post‐fire. To assess the importance of snow cover for revegetation compared to other climatic, topographic, and burn severity‐related variables, binary regression tree models were constructed for the dominant pre‐fire conifer species within each of the four PNW subregions. Summer precipitation consistently appeared as the most important variable driving post‐fire revegetation across all four subregions. Snow cover variables (snow cover frequency and snow disappearance date), along with elevation, were shown to be secondary but significantly influential explanatory variables for revegetation in the Oregon and Washington Cascades. Revegetation was also analyzed using a time series of linear regressions across 200‐m elevation bands by measuring correlations between winter snow cover and summer vegetation greenness. Results showed strong positive post‐fire correlations at moderate elevations in the western Montana Rockies and at the lowest elevation band in the Idaho Rockies. Considering trends of increasing wildfire activity, lower snowpacks, and earlier snow disappearance dates across the PNW, forests will likely experience more frequent drought conditions that will impact post‐wildfire vegetation regrowth.

Distributed cell assemblies spanning prefrontal cortex and striatum

Highly synchronous neuronal assembly activity is deemed essential for cognitive brain function. In theory, such synchrony could coordinate multiple brain areas performing complementary processes. However, cell assemblies have been observed only in single structures, typically cortical areas, and little is known about their synchrony with downstream subcortical structures, such as the striatum. Here, we demonstrate distributed cell assemblies activated at high synchrony (∼10ms) spanning prefrontal cortex and striatum. In addition to including neurons at different brain hierarchical levels, surprisingly, they synchronized functionally distinct limbic and associative sub-regions. These assembly activations occurred when members shifted their firing phase relative to ongoing 4 Hz and theta rhythms, in association with high gamma oscillations. This suggests that these rhythms could mediate the emergence of cross-structural assemblies. To test for the role of assemblies in behavior, we trained the rats to perform a task requiring cognitive flexibility, alternating between two different rules in a T-maze. Overall, assembly activations were correlated with task-relevant parameters, including impending choice, reward, rule, or rule order. Moreover, these behavioral correlates were more robustly expressed by assemblies than by their individual member neurons. Finally, to verify whether assemblies can be endogenously generated, we found that they were indeed spontaneously reactivated during sleep and quiet immobility. Thus, cell assemblies are a more general coding mechanism than previously envisioned, linking distributed neocortical and subcortical areas at high synchrony.

Evidence for two distinct thalamocortical circuits in retrosplenial cortex

Retrosplenial cortex (RSC) lies at the interface between sensory and cognitive networks in the brain and mediates between these, although it is not yet known how. It has two distinct subregions, granular (gRSC) and dysgranular (dRSC). The present study investigated how these subregions differ with respect to their electrophysiology and thalamic connectivity, as a step towards understanding their functions. The gRSC is more closely connected to the hippocampal formation, in which theta-band local field potential oscillations are prominent. We, therefore, compared theta-rhythmic single-unit activity between the two RSC subregions and found, mostly in gRSC, a subpopulation of non-directional cells with spiking activity strongly entrained by theta oscillations, suggesting a stronger coupling of gRSC to the hippocampal system. We then used retrograde tracers to test for differential inputs to RSC from the anteroventral thalamus (AV). We found that gRSC and dRSC differ in their afferents from two AV subfields: dorsomedial (AVDM) and ventrolateral (AVVL). Specifically: (1) as a whole AV projects more strongly to gRSC; (2) AVVL targets both gRSC and dRSC, while AVDM provides a selective projection to gRSC, (3) the gRSC projection is layer-specific: AVDM targets specifically gRSC superficial layers. These same AV projections are topographically organized with ventral AV neurons innervating rostral RSC and dorsal AV neurons innervating caudal RSC. These combined results suggest the existence of two distinct but interacting RSC subcircuits: one connecting AVDM to gRSC that may comprise part of the cognitive hippocampal system, and the other connecting AVVL to both RSC regions that may link hippocampal and perceptual regions. We suggest that these subcircuits are distinct to allow for differential weighting during integration of converging sensory and cognitive computations: an integration that may take place in thalamus, RSC, or both.

Heterogenous electrophysiological responses of functionally distinct striatal subregions to circadian and sleep-related homeostatic processes.

Basal ganglia (BG) are a set of subcortical nuclei that are involved in the control of a wide variety of motor, cognitive, and affective behaviors. Although many behavioral abnormalities associated with BG dysfunction overlap with the clinical picture precipitated by the lack of sleep, the impact of sleep alterations on neuronal activity in BG is unknown. Using wild-type C57BI mice, we investigated the circadian and sleep-related homeostatic modulation of neuronal activity in the three functional subdivisions of the striatum (i.e. sensorimotor, associative, and limbic striatum). We found no circadian modulation of activity in both ventral and dorsomedial striatum while the dorsolateral striatum displayed a significant circadian rhythm with increased firing rates during the subjective dark, active phase. By combining neuronal activity recordings with electroencephalogram (EEG) recordings, we found a strong modulation of neuronal activity by the nature of vigilance states with increased activity during wakefulness and rapid eye movement sleep relative to nonrapid eye movement sleep in all striatal subregions. Depriving animals of sleep for 6 h induced significant, but heterogenous alterations in the neuronal activity across striatal subregions. Notably, these alterations lasted for up to 48 h in the sensorimotor striatum and persisted even after the normalization of cortical EEG power densities. Our results show that vigilance and sleep states as well as their disturbances significantly affect neuronal activity within the striatum. We propose that these changes in neuronal activity underlie both the well-established links between sleep alterations and several disorders involving BG dysfunction as well as the maladaptive changes in behavior induced in healthy participants following sleep loss.

Differential Effects of the Inactivation of Anterior and Posterior Orbitofrontal Cortex on Affective Responses to Proximal and Distal Threat, and Reward Anticipation in the Common Marmoset.

Structural and functional abnormalities of the orbitofrontal cortex (OFC) have been implicated in affective disorders that manifest anxiety-related symptoms. However, research into the functions of primate OFC has predominantly focused on reward-oriented rather than threat-oriented responses. To redress this imbalance, the present study performed a comprehensive analysis of the independent role of 2 distinct subregions of the central OFC (anterior area 11; aOFC and posterior area 13; pOFC) in the processing of distal and proximal threat. Temporary inactivation of both aOFC and pOFC heightened responses to distal threat in the form of an unknown human, but not to proximal threat assessed in a discriminative Pavlovian conditioning task. Inactivation of the aOFC, however, did unexpectedly blunt conditioned threat responses, although the effect was not valence-specific, as conditioned appetitive responses were similarly blunted and appeared restricted to a discriminative version of the task (when both CS− and CS+ are present within a session). Inactivation of the pOFC did not affect conditioned responses to either proximal threat or reward and basal cardiovascular activity was unaffected by manipulations of activity in either subregion. The results highlight the contribution of aOFC and pOFC to regulation of responses to more distal uncertain but not proximal, certain threat and reveal their opposing contribution to that of the immediately adjacent medial OFC, area 14.

On self and mutual winding helicity

The topological underpinning of magnetic fields connected to a planar boundary is naturally described by field line winding. This observation leads to the definition of winding helicity, which is closely related to the more commonly calculated relative helicity. Winding helicity, however, has several advantages, and we explore some of these in this work. In particular, we show, by splitting the domain into distinct subregions, that winding helicity can be decomposed naturally into “self” and “mutual” components and that these quantities can be calculated, in practice, for magnetic fields with complex geometries and topologies. Further, winding provides a unified topological description from which known expressions for self and mutual helicity can be readily derived and generalized. We illustrate the application of calculating self and mutual winding helicities in a simulation of an evolving magnetic field with non-trivial field line topology.

Molecular competition can shape enhancer activity in the Drosophila embryo

SummaryTransgenic reporters allow the measurement of regulatory DNA activity in vivo and consequently have long been useful tools for studying enhancers. Despite their utility, few studies have investigated the effects these reporters may have on the expression of other genes. Understanding these effects is required to accurately interpret reporter data and characterize gene regulatory mechanisms. By measuring the expression of Kruppel (Kr) enhancer reporters in live Drosophila embryos, we find reporters inhibit one another’s expression and that of a nearby endogenous gene. Using synthetic transcription factor (TF) binding site arrays, we present evidence that competition for TFs is partially responsible for the observed transcriptional inhibition. We develop a simple thermodynamic model that predicts competition of the measured magnitude specifically when TF binding is restricted to distinct nuclear subregions. Our findings underline an unexpected role of the non-homogenous nature of the nucleus in regulating gene expression.

A mosaic of cost-benefit control over cortico-striatal circuitry.

Dopamine contributes to cognitive control through well-established effects in both the striatum and cortex. Although earlier work suggests that dopamine affects cognitive control capacity, more recent work suggests that striatal dopamine may also impact on cognitive motivation. We consider the emerging perspective that striatal dopamine boosts control by making people more sensitive to the benefits versus the costs of cognitive effort, and we discuss how this sensitivity shapes competition between controlled and prepotent actions. We propose that dopamine signaling in distinct cortico-striatal subregions mediates different types of cost-benefit tradeoffs, and also discuss mechanisms for the local control of dopamine release, enabling selectivity among cortico-striatal circuits. In so doing, we show how this cost-benefit mosaic can reconcile seemingly conflicting findings about the impact of dopamine signaling on cognitive control.

Differential involvement of hippocampal subfields in Niemann-Pick type C disease: a case-control study.

Hippocampal brain regions are strongly implicated in Niemann Pick type C disease (NPC), but little is known regarding distinct subregions of the hippocampal complex and whether these are equally or differentially affected. To address this gap, we compared volumes of five hippocampal subfields between NPC and healthy individuals using MRI. To this end, 9 adult-onset NPC cases and 9 age- and gender-matched controls underwent a 3T T1-weighted MRI scan. Gray matter volumes of the cornu ammonis (CA1, CA2 and CA3), dentate gyrus (DG), subiculum, entorhinal cortex and hippocampal-amygdalar transition area were calculated by integrating MRI-based image intensities with microscopically defined cytoarchitectonic probabilities. Compared to healthy controls, NPC patients showed smaller volumes of the CA1-3 and DG regions bilaterally, with the greatest difference localized to the left DG (Cohen's d = 1.993, p = 0.008). No significant associations were shown between hippocampal subfield volumes and key clinical features of NPC, including disease duration, symptom severity and psychosis. The pattern of hippocampal subregional atrophy in NPC differs from those seen in other dementias, which may indicate unique cytoarchitectural vulnerabilities in this earlier-onset disorder. Future MRI studies of hippocampal subfields may clarify its potential as a biomarker of neurodegeneration in NPC.

A touch of hierarchy: population receptive fields reveal fingertip integration in Brodmann areas in human primary somatosensory cortex

Several neuroimaging studies have shown the somatotopy of body part representations in primary somatosensory cortex (S1), but the functional hierarchy of distinct subregions in human S1 has not been adequately addressed. The current study investigates the functional hierarchy of cyto-architectonically distinct regions, Brodmann areas BA3, BA1, and BA2, in human S1. During functional MRI experiments, we presented participants with vibrotactile stimulation of the fingertips at three different vibration frequencies. Using population Receptive Field (pRF) modeling of the fMRI BOLD activity, we identified the hand region in S1 and the somatotopy of the fingertips. For each voxel, the pRF center indicates the finger that most effectively drives the BOLD signal, and the pRF size measures the spatial somatic pooling of fingertips. We find a systematic relationship of pRF sizes from lower-order areas to higher-order areas. Specifically, we found that pRF sizes are smallest in BA3, increase slightly towards BA1, and are largest in BA2, paralleling the increase in visual receptive field size as one ascends the visual hierarchy. Additionally, we find that the time-to-peak of the hemodynamic response in BA3 is roughly 0.5 s earlier compared to BA1 and BA2, further supporting the notion of a functional hierarchy of subregions in S1. These results were obtained during stimulation of different mechanoreceptors, suggesting that different afferent fibers leading up to S1 feed into the same cortical hierarchy.

Differential Contribution of Anterior and Posterior Midcingulate Subregions to Distal and Proximal Threat Reactivity in Marmosets.

The midcingulate cortex (MCC) is associated with cognition and emotion regulation. Structural and correlational functional evidence suggests that rather than being homogenous, the MCC may have dissociable functions that can be mapped onto distinct subregions. In this study, we use the marmoset monkey to causally investigate the contributions of two proposed subregions of the MCC: the anterior and posterior midcingulate cortices (aMCC and pMCC) to behavioral and cardiovascular correlates of threat processing relevant to anxiety disorders. Transient inactivation of the aMCC decreased anxiety-like responses to a postencounter distal threat, namely an unfamiliar human intruder, while inactivation of the pMCC showed a mild but opposing effect. Furthermore, although inactivation of neither MCC subregions had any effect on basal cardiovascular activity, aMCC inactivation blunted the expression of both cardiovascular and behavioral conditioned responses to a predictable proximal threat (a rubber snake) during the extinction in a Pavlovian conditioning task, with pMCC inactivation having again an opposing effect, but primarily on the behavioral response. These findings suggest that the MCC is indeed functionally heterogeneous with regards to its role in threat processing, with aMCC providing a marked facilitative contribution to the expression of the emotional response to both proximal and distal threat.