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Background and Purpose: Neonatal hypoxic-ischemic injury of the brain and resultant encephalopathy (HIE) leads to major developmental impairments by school age. Conventional/anatomical MRI often fails to detect hippocampal injury in mild cases. We hypothesize that diffusion tensor imaging (DTI) has greater sensitivity for identifying subtle hippocampal injury.Methods: We retrospectively analyzed DTI data collected from a cohort of neonates with HIE and controls. Conventional MRI sequences were classified qualitatively according to severity using a modified Barkovich scale. Using multivariate linear regression, we compared hippocampal DTI scalars of HIE patients and controls. Spearman correlation was used to test the association of DTI scalars in the hippocampal and thalamic regions. A multiple regression analysis tested the association of the DTI scalars with short-term outcomes.Results: Fifty-five neonates with HIE (42% males) and 13 controls (54% males) were included. Hippocampal DTI scalars were similar between HIE and control groups, even when restricting the HIE group to those with moderate-to-severe injury (8 subjects). DTI scalars of the thalamus were significantly lower in the moderate-to-severely affected patients compared to controls (right fractional anisotropy [FA] .148 vs. .182, P = .01; left FA .147 vs. .181, P = .03). Hippocampal and thalamic DTI scalars were correlated (P < .001). Hippocampal DTI scalars were not associated with short-term outcomes.Conclusions: Quantitative DTI analysis of the hippocampus in neonates following HIE is a feasible technique to examine neuronal injury. Although DTI scalars were useful in identifying thalamic injury in our cohort, hippocampal DTI analysis did not provide additional information regarding hippocampal injury following HIE. [ABSTRACT FROM AUTHOR]

To evaluate permanent effects of hippocampal and prefrontal cortex lesion on spatial tasks, lesioned and sham-operated female C57BL/6 mice were exposed to a series of conditioning schemes in IntelliCages housing 8–10 transponder-tagged mice from each treatment group. Sequential testing started at 51–172 days after bilateral lesions and lasted for 154 and 218 days in two batches of mice, respectively. Spontaneous undisturbed behavioral patterns clearly separated the three groups, hippocampals being characterized by more erratic hyperactivity, and strongly impaired circadian synchronization ability. Hippocampal lesions led to deficits in spatial passive avoidance, as well as in spatial reference and working memory tasks. Impairment was minimal in rewarded preference/reversal schemes, but prominent if behavioral responses required precise circadian timing or included punishment of wrong spatial choices. No differences between sham-operated and prefrontally lesioned subjects in conditioning success were discernible. These results corroborate the view that hippocampal dysfunction spares simple spatial learning tasks but impairs the ability to cope with conflicting task-inherent spatial, temporal or emotional cues. Methodologically, the results show that automated testing and data analysis of socially kept mice is a powerful, efficient and animal-friendly tool for dissecting complex features and behavioral profiles of hippocampal dysfunction characterizing many transgenic or pharmacological mouse models. [ABSTRACT FROM AUTHOR]

The hippocampal formation is involved in navigation, and its neuronal activity exhibits a variety of spatial correlates (e.g., place cells, grid cells). The quantification of the information encoded by spikes has been standard procedure to identify which cells have spatial correlates. For place cells, most of the established metrics derive from Shannon’s mutual information (Shannon, 1948), and convey information rate in bits/s or bits/spike (Skaggs et al., 1993, 1996). Despite their widespread use, the performance of these metrics in relation to the original mutual information metric has never been investigated. In this work, using simulated and real data, we find that the current information metrics correlate less with the accuracy of spatial decoding than the original mutual information metric. We also find that the top informative cells may differ among metrics, and show a surrogate-based normalization that yields comparable spatial information estimates. Since different information metrics may identify different neuronal populations, we discuss current and alternative definitions of spatially informative cells, which affect the metric choice. [ABSTRACT FROM AUTHOR]

Objective: Research has shown that depression is a risk factor for Alzheimer's disease (AD) and subsequent cognitive decline. This is compounded by evidence showing an association between depression and reduced hippocampal volumes; a primary structure implicated in the pathogenesis of the disease. Less is known about the relationship between depression and other AD vulnerable regions such as the entorhinal cortex. Given the heterogeneity of depressive symptom presentation, we examined whether symptom dimensions were associated with hippocampal and entorhinal cortex volumes in community dwelling older adults. Methods: Eighty-one community dwelling adults completed the Beck Depression Inventory - second edition and underwent structural neuroimaging. Measures of hippocampal and entorhinal cortex volumes were obtained using FreeSurfer software. Linear regression models included regions of interest as dependent variables, with depressive symptom dimensions, as independent variables, controlling for total intracranial volumes, age, education, and gender. Results: Somatic symptoms were negatively associated with total, right, and left hippocampal volumes. Affective symptoms were negatively associated with total entorhinal cortex volumes, with a marginal main effect on left entorhinal cortex volumes. Conclusion: Our findings provide support for examining depressive symptoms and their association with AD vulnerable regions along subdimensions of affective, cognitive, and somatic symptoms to better understand profiles of symptoms most associated with these regions. Conceptualizing depressive symptoms in this way may also better inform treatment approaches in terms of targeting types of symptoms that may be more closely linked to poorer brain and cognitive health outcomes. [ABSTRACT FROM AUTHOR]

Acetylcholine (ACh) is believed to act as a neuromodulator in cortical circuits that support cognition, specifically in processes including learning, memory consolidation, vigilance, arousal and attention. The cholinergic modulation of cortical processes is studied in many model systems including rodents, cats and primates. Further, these studies are performed in cortical areas ranging from the primary visual cortex to the prefrontal cortex and using diverse methodologies. The results of these studies have been combined into singular models of function--a practice based on an implicit assumption that the various model systems are equivalent and interchangeable. However, comparative anatomy both within and across species reveals important differences in the structure of the cholinergic system. Here, we will review anatomical data including innervation patterns, receptor expression, synthesis and release compared across species and cortical area with a focus on rodents and primates. We argue that these data suggest no canonical cortical model system exists for the cholinergic system. Further, we will argue that as a result, care must be taken both in combining data from studies across cortical areas and species, and in choosing the best model systems to improve our understanding and support of human health. [ABSTRACT FROM AUTHOR]

The hippocampus contains place cells representing spaces in an environment, and these place cells have been suggested to play a fundamental role in the formation of a cognitive map for spatial processing. However, how alterations in the firing patterns of place cells in response to aversive events encode the locations tied to these aversive events is unknown. Here, we analyzed spiking patterns of place cell ensembles in the dorsal hippocampal CA1 region of rats performing a T-maze alternation task with an aversive air-puff stimulation applied at a specific location on one side of a trajectory. The intensity of the air puff was adjusted so that the rats decreased their running speed before passing the aversive location. The addition of the aversive stimulus induced reorganization of place cell ensembles on both left and right trajectories with and without the aversive stimulus, respectively. Specifically, the animals showed a more abundant spatial representation in the vicinity of the aversive location. Removing the aversive stimulus induced new spatial firing patterns on both of the trajectories that differed from those both before and during application of the aversive stimulus. These results demonstrate that hippocampal spatial maps are flexibly reorganized to represent particular aversive events. [ABSTRACT FROM AUTHOR]

Concurrent with mental processes that require rigorous computation and control, a series of automated decisions and actions govern our daily lives, providing efficient and adaptive responses to environmental demands. Using a cognitive flexibility task, we show that a set of brain regions collectively known as the default mode network plays a crucial role in such "autopilot" behavior, i.e., when rapidly selecting appropriate responses under predictable behavioral contexts. While applying learned rules, the default mode network shows both greater activity and connectivity. Furthermore, functional interactions between this network and hippocampal and parahippocampal areas as well as primary visual cortex correlate with the speed of accurate responses. These findings indicate a memory-based "autopilot role" for the default mode network, which may have important implications for our current understanding of healthy and adaptive brain processing. [ABSTRACT FROM AUTHOR]

Prior research has identified age-by-valence interactions in both behavior and neural recruitment; age has been associated with increased retrieval of positive relative to negative information as well as an increased tendency to recruit prefrontal regions during negative event retrieval and for this recruitment to correspond to decreased hippocampal connectivity. To date, the explicit relation between prefrontal recruitment and memory phenomenology has not been examined. The current study examined the link between these two measures by examining age-by-valence interactions in the relation between prefrontal recruitment and subjective ratings of memory vividness. Participants (ages 18–85) encoded visual images paired with verbal titles. During a scanned retrieval session, they were presented with titles and asked whether each had been seen with an image during encoding. Participants provided vividness ratings following retrieval of each image. Age was associated with greater prefrontally-mediated alterations in negative event phenomenology, with age-related increases in the relation between ventral prefrontal regions and negative event vividness and age-related decreases in the relation between dorsal prefrontal regions and negative event vividness. This analysis confirmed a critical role of PFC regions in age-by-valence interactions, where age reversed the relation between PFC recruitment and the subjective richness of retrieved memory representation. These findings are consistent with studies that reveal age-related enhancements in emotion regulation, and suggest that older adults may be engaging in these processes during retrieval of negative events. [ABSTRACT FROM AUTHOR]

Left–right asymmetry is a fundamental feature of higher-order brain structure; however, the molecular basis of brain asymmetry remains unclear. We recently identified structural and functional asymmetries in mouse hippocampal circuitry that result from the asymmetrical distribution of two distinct populations of pyramidal cell synapses that differ in the density of the NMDA receptor subunit GluRε2 (also known as NR2B, GRIN2B or GluN2B). By examining the synaptic distribution of ε2 subunits, we previously found that β2-microglobulin-deficient mice, which lack cell surface expression of the vast majority of major histocompatibility complex class I (MHCI) proteins, do not exhibit circuit asymmetry. In the present study, we conducted electrophysiological and anatomical analyses on the hippocampal circuitry of mice with a knockout of the paired immunoglobulin-like receptor B (PirB), an MHCI receptor. As in β2-microglobulin-deficient mice, the PirB-deficient hippocampus lacked circuit asymmetries. This finding that MHCI loss-of-function mice and PirB knockout mice have identical phenotypes suggests that MHCI signals that produce hippocampal asymmetries are transduced through PirB. Our results provide evidence for a critical role of the MHCI/PirB signaling system in the generation of asymmetries in hippocampal circuitry. [ABSTRACT FROM AUTHOR]

A neural synchrony model of cognitive control is proposed. It construes cognitive control as a higher-level action to synchronize lower-level brain areas. Here, a controller prefrontal area (medial frontal cortex) can synchronize two cortical processing areas. The synchrony is achieved by a randomtheta frequency-locked neural burst sent to both areas. The choice of areas that receive this burst is determined by lateral frontal cortex. As a result of this synchrony, communication between the two areas becomes more efficient. The model is tested on the classical Stroop cognitive control task, and its operation is explored in several simulations. Both reactive and proactive controls are implemented via theta power modulation. Increasing theta power improves behavioral performance; furthermore, via theta-gamma phase-amplitude coupling, theta also increases gamma frequency power and synchrony in posterior processing areas. Thus, the model solves a central computational problem for cognitive control (how to allow rapid communication between arbitrary brain areas), while making rich contact with behavioral and neurophysiological data. [ABSTRACT FROM AUTHOR]

Abstract: The conductivity profile of the head has a major effect on EEG signals, but unfortunately the conductivity for the most important compartment, skull, is only poorly known. In dipole modeling studies, errors in modeled skull conductivity have been considered to have a detrimental effect on EEG source estimation. However, as dipole models are very restrictive, those results cannot be generalized to other source estimation methods. In this work, we studied the sensitivity of EEG and combined MEG+EEG source estimation to errors in skull conductivity using a distributed source model and minimum-norm (MN) estimation. We used a MEG/EEG modeling set-up that reflected state-of-the-art practices of experimental research. Cortical surfaces were segmented and realistically-shaped three-layer anatomical head models were constructed, and forward models were built with Galerkin boundary element method while varying the skull conductivity. Lead-field topographies and MN spatial filter vectors were compared across conductivities, and the localization and spatial spread of the MN estimators were assessed using intuitive resolution metrics. The results showed that the MN estimator is robust against errors in skull conductivity: the conductivity had a moderate effect on amplitudes of lead fields and spatial filter vectors, but the effect on corresponding morphologies was small. The localization performance of the EEG or combined MEG+EEG MN estimator was only minimally affected by the conductivity error, while the spread of the estimate varied slightly. Thus, the uncertainty with respect to skull conductivity should not prevent researchers from applying minimum norm estimation to EEG or combined MEG+EEG data. Comparing our results to those obtained earlier with dipole models shows that general judgment on the performance of an imaging modality should not be based on analysis with one source estimation method only. [Copyright &y& Elsevier]

Highlights: [•] We demonstrate that water immersion (WI) modulates sensorimotor integration as indicated by decreased short- and long-latency afferent inhibition. [•] WI did not change corticospinal excitability, short-interval intracortical inhibition, or intracortical facilitation. [•] A greater understanding of the neurophysiological effects of WI could lead to more efficacious use of aquatic therapy in rehabilitation regimens. [ABSTRACT FROM AUTHOR]

Highlights: [•] Virtual reality (VR) and EEG were used to investigate the effect of visual perturbation on standing posture. [•] Whole body postural responses were not different between predictable and unpredictable conditions. [•] Unpredictable timing and direction of perturbation. [ABSTRACT FROM AUTHOR]

The authors discuss the roles of the mature granule cell population in the dentate gyrus with respect to adult neurogenesis. The properties and functions of adult-born granule cells in memory encoding are outlined. The innervation of the dentate gyrus by reelinergic afferents from the entorhinal cortex is highlighted.

Topographic maps of the receptive surface are a fundamental feature of neural organization in many sensory systems. While touch is finely mapped in the cerebral cortex, it remains controversial how precise any cortical nociceptive map may be. Given that nociceptive innervation density is relatively low on distal skin regions such as the digits, one might conclude that the nociceptive system lacks fine representation of these regions. Indeed, only gross spatial organization of nociceptive maps has been reported so far. However, here we reveal the existence of fine-grained somatotopy for nociceptive inputs to the digits in human primary somatosensory cortex (SI). Using painful nociceptive-selective laser stimuli to the hand, and phase-encoded functional magnetic resonance imaging analysis methods, we observed somatotopic maps of the digits in contralateral SI. These nociceptive maps were highly aligned with maps of non-painful tactile stimuli, suggesting comparable cortical representations for, and possible interactions between, mechanoreceptive and nociceptive sig-nals. Our findings may also be valuable for future studies tracking the time course and the spatial pattern of plastic changes in cortical organization involved in chronic pain. [ABSTRACT FROM AUTHOR]

Abstract: Hyperoside is a flavonoid compound and widely used in clinic to relieve pain and improve cardiovascular functions. However, the effects of hyperoside on ischemic neurons and the molecular mechanisms remain unclear. Here, we used an in vitro ischemic model of oxygen–glucose deprivation followed by reperfusion (OGD-R) to investigate the protective effects of hyperoside on ischemic neuron injury and further explore the possible related mechanisms. Our results demonstrated that hyperoside protected cultured cortical neurons from OGD-R injury, it also relieved glutamate-induced neuronal injury and NMDA-induced [Ca2+]i elevation. As for the mechanisms, hyperoside firstly attenuated the phosphorylation of CaMKII caused by OGD-R lesions. Meanwhile, hyperoside lessened iNOS expression induced by OGD-R via inhibition of NF-κB activation. Furthermore, ameliorating of ERK, JNK and Bcl-2 family-related apoptotic signaling pathways were also involved in the neuroprotection of hyperoside. Taken together, these studies revealed that hyperoside had protective effects on neuronal ischemia-reperfusion impairment, which was related to the regulation of nitric oxide signaling pathway. [Copyright &y& Elsevier]

Abstract: Physiological results for the size of face-specific units in inferotemporal cortex (IT) support an extraordinarily large range of possible sizes—from 2.5° to 30° or more. We use a behavioral test of face-specific aftereffects to measure the face analysis regions and find a coarse retinotopy consistent with receptive fields of intermediate size (10°–12° at 3° eccentricity). In the first experiment, observers were adapted to a single face at 3° from fixation. A test (a morph of the face and its anti-face) was then presented at different locations around fixation and subjects classified it as face or anti-face. The face aftereffect (FAE) was not constant at all test locations—it dropped to half its maximum value for tests 5° from the adapting location. Simultaneous adaptation to both a face and its anti-face, placed at opposite locations across fixation, produced two separate regions of opposite aftereffects. However, with four stimuli, faces alternating with anti-faces equally spaced around fixation, the FAE was greatly reduced at all locations, implying a fairly coarse localization of the aftereffect. In the second experiment, observers adapted to a face and its anti-face presented either simultaneously or in alternation. Results showed that the simultaneous presentation of a face and its anti-face leads to stronger FAEs than sequential presentation, suggesting that face processing has a dynamic nature and its region of analysis is sharpened when there is more than one face in the scene. In the final experiment, a face and two anti-face flankers with different spatial offsets were presented during adaptation and the FAE was measured at the face location. Results showed that FAE at the face location was inhibited more as the distance of anti-face flankers to the face stimulus was reduced. This confirms the spatial extent of face analysis regions in a test with a fixed number of stimuli where only distance varied. [Copyright &y& Elsevier]

Background: The cerebral cortex is divisible into many individual areas, each exhibiting distinct connectivity profiles, architecture, and physiological characteristics. Interactions among cortical areas underlie higher sensory, motor, and cognitive functions. Graph theory provides an important framework for understanding network properties of the interareal weighted and directed connectiv-ity matrix reported in recent studies. Advances: We derive an exponential distance rule that predicts many binary and weighted features of the cortical network, including efficiency of information transfer, the high specificity of long-distance compared to short-distance connections, wire length minimization, and the existence of a highly interconnected cortical core. We propose a bow-tie representation of the cortex, which combines these features with hierarchical processing. Outlook: The exponential distance rule has important implications for understanding scaling prop-erties of the cortex and developing future large-scale dynamic models of the cortex. [ABSTRACT FROM AUTHOR]