Encoding of Visual Objects in the Human Medial Temporal Lobe.

The human medial temporal lobe (MTL) plays a crucial role in recognizing visual objects, a key cognitive function that relies on the formation of semantic representations. Nonetheless, it remains unknown how visual information of general objects is translated into semantic representations in the MTL. Furthermore, the debate about whether the human MTL is involved in perception has endured for a long time. To address these questions, we investigated three distinct models of neural object coding-semantic coding, axis-based feature coding, and region-based feature coding-in each subregion of the human MTL, using high-resolution fMRI in two male and six female participants. Our findings revealed the presence of semantic coding throughout the MTL, with a higher prevalence observed in the parahippocampal cortex (PHC) and perirhinal cortex (PRC), while axis coding and region coding were primarily observed in the earlier regions of the MTL. Moreover, we demonstrated that voxels exhibiting axis coding supported the transition to region coding and contained information relevant to semantic coding. Together, by providing a detailed characterization of neural object coding schemes and offering a comprehensive summary of visual coding information for each MTL subregion, our results not only emphasize a clear role of the MTL in perceptual processing but also shed light on the translation of perception-driven representations of visual features into memory-driven representations of semantics along the MTL processing pathway.

Contribution of the lateral occipital and parahippocampal cortices to pattern separation of objects and contexts.

Contextual features are integral to episodic memories; yet, we know little about context effects on pattern separation, a hippocampal function promoting orthogonalization of overlapping memory representations. Recent studies suggested that various extrahippocampal brain regions support pattern separation; however, the specific role of the parahippocampal cortex-a region involved in context representation-in pattern separation has not yet been studied. Here, we investigated the contribution of the parahippocampal cortex (specifically, the parahippocampal place area) to context reinstatement effects on mnemonic discrimination, using functional magnetic resonance imaging. During scanning, participants saw object images on unique context scenes, followed by a recognition task involving the repetitions of encoded objects or visually similar lures on either their original context or a lure context. Context reinstatement at retrieval improved item recognition but hindered mnemonic discrimination. Crucially, our region of interest analyses of the parahippocampal place area and an object-selective visual area, the lateral occipital cortex indicated that while during successful mnemonic decisions parahippocampal place area activity decreased for old contexts compared to lure contexts irrespective of object novelty, lateral occipital cortex activity differentiated between old and lure objects exclusively. These results imply that pattern separation of contextual and item-specific memory features may be differentially aided by scene and object-selective cortical areas.

Comparison of histological delineations of medial temporal lobe cortices by four independent neuroanatomy laboratories.

The medial temporal lobe (MTL) cortex, located adjacent to the hippocampus, is crucial for memory and prone to the accumulation of certain neuropathologies such as Alzheimer's disease neurofibrillary tau tangles. The MTL cortex is composed of several subregions which differ in their functional and cytoarchitectonic features. As neuroanatomical schools rely on different cytoarchitectonic definitions of these subregions, it is unclear to what extent their delineations of MTL cortex subregions overlap. Here, we provide an overview of cytoarchitectonic definitions of the entorhinal and parahippocampal cortices as well as Brodmann areas (BA) 35 and 36, as provided by four neuroanatomists from different laboratories, aiming to identify the rationale for overlapping and diverging delineations. Nissl-stained series were acquired from the temporal lobes of three human specimens (two right and one left hemisphere). Slices (50 µm thick) were prepared perpendicular to the long axis of the hippocampus spanning the entire longitudinal extent of the MTL cortex. Four neuroanatomists annotated MTL cortex subregions on digitized slices spaced 5 mm apart (pixel size 0.4 µm at 20× magnification). Parcellations, terminology, and border placement were compared among neuroanatomists. Cytoarchitectonic features of each subregion are described in detail. Qualitative analysis of the annotations showed higher agreement in the definitions of the entorhinal cortex and BA35, while the definitions of BA36 and the parahippocampal cortex exhibited less overlap among neuroanatomists. The degree of overlap of cytoarchitectonic definitions was partially reflected in the neuroanatomists' agreement on the respective delineations. Lower agreement in annotations was observed in transitional zones between structures where seminal cytoarchitectonic features are expressed less saliently. The results highlight that definitions and parcellations of the MTL cortex differ among neuroanatomical schools and thereby increase understanding of why these differences may arise. This work sets a crucial foundation to further advance anatomically-informed neuroimaging research on the human MTL cortex.

Comparison of head direction cell firing characteristics across thalamo-parahippocampal circuitry.

Head direction (HD) cells, which fire persistently when an animal's head is pointed in a particular direction, are widely thought to underlie an animal's sense of spatial orientation and have been identified in several limbic brain regions. Robust HD cell firing is observed throughout the thalamo-parahippocampal system, although recent studies report that parahippocampal HD cells exhibit distinct firing properties, including conjunctive aspects with other spatial parameters, which suggest they play a specialized role in spatial processing. Few studies, however, have quantified these apparent differences. Here, we performed a comparative assessment of HD cell firing characteristics across the anterior dorsal thalamus (ADN), postsubiculum (PoS), parasubiculum (PaS), medial entorhinal (MEC), and postrhinal (POR) cortices. We report that HD cells with a high degree of directional specificity were observed in all five brain regions, but ADN HD cells display greater sharpness and stability in their preferred directions, and greater anticipation of future headings compared to parahippocampal regions. Additional analysis indicated that POR HD cells were more coarsely modulated by other spatial parameters compared to PoS, PaS, and MEC. Finally, our analyses indicated that the sharpness of HD tuning decreased as a function of laminar position and conjunctive coding within the PoS, PaS, and MEC, with cells in the superficial layers along with conjunctive firing properties showing less robust directional tuning. The results are discussed in relation to theories of functional organization of HD cell tuning in thalamo-parahippocampal circuitry.

Cardiorespiratory fitness is associated with cortical thickness of medial temporal brain areas associated with spatial cognition in young but not older adults.

Cardiorespiratory fitness has a potent effect on neurocognitive health, especially regarding the hippocampal memory system. However, less is known about the impact of cardiorespiratory fitness on medial temporal lobe extrahippocampal neocortical regions. Specifically, it is unclear how cardiorespiratory fitness modulates these brain regions in young adulthood and if these regions are differentially related to cardiorespiratory fitness in young versus older adults. The primary goal of this study was to investigate if cardiorespiratory fitness predicted medial temporal lobe cortical thickness which, with the hippocampus, are critical for spatial learning and memory. Additionally, given the established role of these cortices in spatial navigation, we sought to determine if cardiorespiratory fitness and medial temporal lobe cortical thickness would predict greater subjective sense of direction in both young and older adults. Cross-sectional data from 56 young adults (20-35 years) and 44 older adults (55-85 years) were included. FreeSurfer 6.0 was used to automatically segment participants' 3T T1-weighted images. Using hierarchical multiple regression analyses, we confirmed significant associations between greater cardiorespiratory fitness and greater left entorhinal, left parahippocampal, and left perirhinal cortical thickness in young, but not older, adults. Left parahippocampal cortical thickness interacted with age group to differentially predict subjective sense of direction in young and older adults. Young adults displayed a positive, and older adults a negative, correlation between left parahippocampal cortical thickness and sense of direction. Our findings extend previous work on the association between cardiorespiratory fitness and hippocampal subfield structure in young adults to left medial temporal lobe neocortical regions.

TLR2 immunotherapy suppresses neuroinflammation, tau spread, and memory loss in rTg4510 mice.

In Alzheimer's disease, chronic neuroinflammation is accompanied by amyloid and tau pathologies. Especially, aberrant microglial activation is known to precede the regional tau pathology development, but the mechanisms how microglia affect tau spread remain largely unknown. Here, we found that toll-like receptor 2 (TLR2) in microglia recognizes oligomeric tau as a pathogenic ligand and induces inflammatory responses. Knockout of TLR2 reduced tau pathology and microglial activation in rTg4510 tau transgenic mice. Treatment of oligomeric tau induced TLR2 activation and increased inflammatory responses in microglial cells. TLR2 further mediated the tau-induced microglial activation and promoted tau uptake into neurons in neuron-microglia co-culture system and in mouse hippocampus after intracranial tau injection. Importantly, treatment with anti-TLR2 monoclonal antibody Tomaralimab blocked TLR2 activation and inflammatory responses in a dose-dependent manner, and significantly reduced tau spread and memory loss in rTg4510 mice. These results suggest that TLR2 plays a crucial role in tau spread by causing aberrant microglial activation in response to pathological tau, and blocking TLR2 with immunotherapy may ameliorate tau pathogenesis in Alzheimer's disease.

Scene-selective brain regions respond to embedded objects of a scene.

Objects are fundamental to scene understanding. Scenes are defined by embedded objects and how we interact with them. Paradoxically, scene processing in the brain is typically discussed in contrast to object processing. Using the BOLD5000 dataset (Chang et al., 2019), we examined whether objects within a scene predicted the neural representation of scenes, as measured by functional magnetic resonance imaging in humans. Stimuli included 1,179 unique scenes across 18 semantic categories. Object composition of scenes were compared across scene exemplars in different semantic scene categories, and separately, in exemplars of the same scene category. Neural representations in scene- and object-preferring brain regions were significantly related to which objects were in a scene, with the effect at times stronger in the scene-preferring regions. The object model accounted for more variance when comparing scenes within the same semantic category to scenes from different categories. Here, we demonstrate the function of scene-preferring regions includes the processing of objects. This suggests visual processing regions may be better characterized by the processes, which are engaged when interacting with the stimulus kind, such as processing groups of objects in scenes, or processing a single object in our foreground, rather than the stimulus kind itself.

Generalization of cognitive maps across space and time.

Prominent theories posit that associative memory structures, known as cognitive maps, support flexible generalization of knowledge across cognitive domains. Here, we evince a representational account of cognitive map flexibility by quantifying how spatial knowledge formed one day was used predictively in a temporal sequence task 24 hours later, biasing both behavior and neural response. Participants learned novel object locations in distinct virtual environments. After learning, hippocampus and ventromedial prefrontal cortex (vmPFC) represented a cognitive map, wherein neural patterns became more similar for same-environment objects and more discriminable for different-environment objects. Twenty-four hours later, participants rated their preference for objects from spatial learning; objects were presented in sequential triplets from either the same or different environments. We found that preference response times were slower when participants transitioned between same- and different-environment triplets. Furthermore, hippocampal spatial map coherence tracked behavioral slowing at the implicit sequence transitions. At transitions, predictive reinstatement of virtual environments decreased in anterior parahippocampal cortex. In the absence of such predictive reinstatement after sequence transitions, hippocampus and vmPFC responses increased, accompanied by hippocampal-vmPFC functional decoupling that predicted individuals' behavioral slowing after a transition. Collectively, these findings reveal how expectations derived from spatial experience generalize to support temporal prediction.

Prenatal protein malnutrition decreases neuron numbers in the parahippocampal region but not prefrontal cortex in adult rats.

OBJECTIVE: Prenatal protein malnutrition produces anatomical and functional changes in the developing brain that persist despite immediate postnatal nutritional rehabilitation. Brain networks of prenatally malnourished animals show diminished activation of prefrontal areas and an increased activation of hippocampal regions during an attentional task [1]. While a reduction in cell number has been documented in hippocampal subfield CA1, nothing is known about changes in neuron numbers in the prefrontal or parahippocampal cortices. METHODS: In the present study, we used unbiased stereology to investigate the effect of prenatal protein malnutrition on the neuron numbers in the medial prefrontal cortex and the cortices of the parahippocampal region that comprise the larger functional network. RESULTS: Results show that prenatal protein malnutrition does not cause changes in the neuronal population in the medial prefrontal cortex of adult rats, indicating that the decrease in functional activation during attentional tasks is not due to a reduction in the number of neurons. Results also show that prenatal protein malnutrition is associated with a reduction in neuron numbers in specific parahippocampal subregions: the medial entorhinal cortex and presubiculum. DISCUSSION: The affected regions along with CA1 comprise a tightly interconnected circuit, suggesting that prenatal malnutrition confers a vulnerability to specific hippocampal circuits. These findings are consistent with the idea that prenatal protein malnutrition produces a reorganization of structural and functional networks, which may underlie observed alterations in attentional processes and capabilities.

Entorhinal vessel density correlates with phosphorylated tau and TDP-43 pathology.

INTRODUCTION: The entorhinal cortex (EC) and perirhinal cortex (PC) are vulnerable to Alzheimer's disease. A triggering factor may be the interaction of vascular dysfunction and tau pathology. METHODS: We imaged post mortem human tissue at 100 µm3 with 7 T magnetic resonance imaging and manually labeled individual blood vessels (mean = 270 slices/case). Vessel density was quantified and compared per EC subfield, between EC and PC, and in relation to tau and TAR DNA-binding protein 43 (TDP-43) semiquantitative scores. RESULTS: PC was more vascularized than EC and vessel densities were higher in posterior EC subfields. Tau and TDP-43 strongly correlated with vasculature density and subregions with severe tau at the preclinical stage had significantly greater vessel density than those with low tau burden. DISCUSSION: These data impact cerebrovascular maps, quantification of subfield vasculature, and correlation of vasculature and pathology at early stages. The ordered association of vessel density, and tau or TDP-43 pathology, may be exploited in a predictive context. HIGHLIGHTS: Vessel density correlates with phosphorylated tau (p-tau) burden in entorhinal and perirhinal cortices. Perirhinal area 35 and posterior entorhinal cortex showed greatest p-tau burden but also the highest vessel density in the preclinical phase of Alzheimer's disease. We combined an ex vivo magnetic resonance imaging model and histopathology to demonstrate the 3D reconstruction of intracortical vessels and its spatial relationship to the pathology.

A stimulus-driven approach reveals vertical luminance gradient as a stimulus feature that drives human cortical scene selectivity.

Human neuroimaging studies have revealed a dedicated cortical system for visual scene processing. But what is a "scene"? Here, we use a stimulus-driven approach to identify a stimulus feature that selectively drives cortical scene processing. Specifically, using fMRI data from BOLD5000, we examined the images that elicited the greatest response in the cortical scene processing system, and found that there is a common "vertical luminance gradient" (VLG), with the top half of a scene image brighter than the bottom half; moreover, across the entire set of images, VLG systematically increases with the neural response in the scene-selective regions (Study 1). Thus, we hypothesized that VLG is a stimulus feature that selectively engages cortical scene processing, and directly tested the role of VLG in driving cortical scene selectivity using tightly controlled VLG stimuli (Study 2). Consistent with our hypothesis, we found that the scene-selective cortical regions-but not an object-selective region or early visual cortex-responded significantly more to images of VLG over control stimuli with minimal VLG. Interestingly, such selectivity was also found for images with an "inverted" VLG, resembling the luminance gradient in night scenes. Finally, we also tested the behavioral relevance of VLG for visual scene recognition (Study 3); we found that participants even categorized tightly controlled stimuli of both upright and inverted VLG to be a place more than an object, indicating that VLG is also used for behavioral scene recognition. Taken together, these results reveal that VLG is a stimulus feature that selectively engages cortical scene processing, and provide evidence for a recent proposal that visual scenes can be characterized by a set of common and unique visual features.

Limbic and olfactory cortical circuits in focal seizures.

Epilepsies affecting the limbic regions are common and generate seizures often resistant to pharmacological treatment. Clinical evidence demonstrates that diverse regions of the mesial portion of the temporal lobe participate in limbic seizures; these include the hippocampus, the entorhinal, perirhinal and parahippocampal regions and the piriform cortex. The network mechanisms involved in the generation of olfactory-limbic epileptiform patterns will be here examined, with particular emphasis on acute interictal and ictal epileptiform discharges obtained by treatment with pro-convulsive drugs and by high-frequency stimulations on in vitro preparations, such as brain slices and the isolated guinea pig brain. The interactions within olfactory-limbic circuits can be summarized as follows: independent, region-specific seizure-like events (SLE) are generated in the olfactory and in the limbic cortex; SLEs generated in the hippocampal-parahippocampal regions tend to remain within these areas; the perirhinal region controls the neocortical propagation and the generalization of limbic seizures; interictal spiking in the olfactory regions prevents the invasion by SLEs generated in limbic regions. The potential relevance of these observations for human focal epilepsy is discussed.

Superficial-layer versus deep-layer lateral entorhinal cortex: Coding of allocentric space, egocentric space, speed, boundaries, and corners.

Entorhinal cortex is the major gateway between the neocortex and the hippocampus and thus plays an essential role in subserving episodic memory and spatial navigation. It can be divided into the medial entorhinal cortex (MEC) and the lateral entorhinal cortex (LEC), which are commonly theorized to be critical for spatial (context) and non-spatial (content) inputs, respectively. Consistent with this theory, LEC neurons are found to carry little information about allocentric self-location, even in cue-rich environments, but they exhibit egocentric spatial information about external items in the environment. The superficial and deep layers of LEC are believed to mediate the input to and output from the hippocampus, respectively. As earlier studies mainly examined the spatial firing properties of superficial-layer LEC neurons, here we characterized the deep-layer LEC neurons and made direct comparisons with their superficial counterparts in single unit recordings from behaving rats. Because deep-layer LEC cells received inputs from hippocampal regions, which have strong selectivity for self-location, we hypothesized that deep-layer LEC neurons would be more informative about allocentric position than superficial-layer LEC neurons. We found that deep-layer LEC cells showed only slightly more allocentric spatial information and higher spatial consistency than superficial-layer LEC cells. Egocentric coding properties were comparable between these two subregions. In addition, LEC neurons demonstrated preferential firing at lower speeds, as well as at the boundary or corners of the environment. These results suggest that allocentric spatial outputs from the hippocampus are transformed in deep-layer LEC into the egocentric coding dimensions of LEC, rather than maintaining the allocentric spatial tuning of the CA1 place fields.

A model for transforming egocentric views into goal-directed behavior.

Neurons in the rat postrhinal cortex (POR) respond to the egocentric (observer-centered) bearing and distance of the boundaries, or geometric center, of an enclosed space. Understanding of the precise geometric and sensory properties of the environment that generate these signals is limited. Here we model how this signal may relate to visual perception of motion parallax along environmental boundaries. A behavioral extension of this tuning is the known 'centering response', in which animals follow a spatial gradient function based on boundary parallax to guide behavior toward the center of a corridor or enclosure. Adding an allocentric head direction signal to this representation can translate the gradient across two-dimensional space and provide a new gradient for directing behavior to any location. We propose a model for how this signal may support goal-directed navigation via projections to the dorsomedial striatum. The result is a straightforward code for navigational variables derived from visual geometric properties of the surrounding environment, which may be used to map space and transform incoming sensory information into an appropriate motor output.

Organization of projections from the entorhinal cortex to the hippocampal formation of the Egyptian fruit bat Rousettus aegyptiacus.

The hippocampal formation and entorhinal cortex are crucially involved in learning and memory as well as in spatial navigation. The conservation of these structures across the entire mammalian lineage demonstrates their importance. Information on a diverse set of spatially tuned neurons has become available, but we only have a rudimentary understanding of how anatomical network structure affects functional tuning. Bats are the only order of mammals that have evolved true flight, and with this specialization comes the need to navigate and behave in a three dimensional (3D) environment. Spatial tuning of cells in the entorhinal-hippocampal network of bats has been studied for some time, but whether the reported tuning in 3D is associated with changes in the entorhinal-hippocampal network is not known. Here we investigated the entorhinal-hippocampal projections in the Egyptian fruit bat (Rousettus aegyptiacus), by injecting chemical anterograde tracers in the entorhinal cortex. Detailed analyses of the terminations of these projections in the hippocampus showed that both the medial and lateral entorhinal cortex sent projections to the molecular layer of all subfields of the hippocampal formation. Our analyses showed that the terminal distributions of entorhinal fibers in the hippocampal formation of Egyptian fruit bats-including the proximo-distal and longitudinal topography and the layer-specificity-are similar to what has been described in other mammalian species such as rodents and primates. The major difference in entorhinal-hippocampal projections that was described to date between rodents and primates is in the terminal distribution of the DG projection. We found that bats have entorhinal-DG projections that seem more like those in primates than in rodents. It is likely that the latter projection in bats is specialized to the behavioral needs of this species, including 3D flight and long-distance navigation.

Hippocampal spatial view cells for memory and navigation, and their underlying connectivity in humans.

Hippocampal and parahippocampal gyrus spatial view neurons in primates respond to the spatial location being looked at. The representation is allocentric, in that the responses are to locations "out there" in the world, and are relatively invariant with respect to retinal position, eye position, head direction, and the place where the individual is located. The underlying connectivity in humans is from ventromedial visual cortical regions to the parahippocampal scene area, leading to the theory that spatial view cells are formed by combinations of overlapping feature inputs self-organized based on their closeness in space. Thus, although spatial view cells represent "where" for episodic memory and navigation, they are formed by ventral visual stream feature inputs in the parahippocampal gyrus in what is the parahippocampal scene area. A second "where" driver of spatial view cells are parietal inputs, which it is proposed provide the idiothetic update for spatial view cells, used for memory recall and navigation when the spatial view details are obscured. Inferior temporal object "what" inputs and orbitofrontal cortex reward inputs connect to the human hippocampal system, and in macaques can be associated in the hippocampus with spatial view cell "where" representations to implement episodic memory. Hippocampal spatial view cells also provide a basis for navigation to a series of viewed landmarks, with the orbitofrontal cortex reward inputs to the hippocampus providing the goals for navigation, which can then be implemented by hippocampal connectivity in humans to parietal cortex regions involved in visuomotor actions in space. The presence of foveate vision and the highly developed temporal lobe for object and scene processing in primates including humans provide a basis for hippocampal spatial view cells to be key to understanding episodic memory in the primate and human hippocampus, and the roles of this system in primate including human navigation.

Hippocampal spatial view cells, place cells, and concept cells: View representations.

A commentary is provided on issues raised in the Special Issue of Hippocampus (2023) on hippocampal system view representations. First, the evidence for hippocampal and parahippocampal spatial view cells in primates including humans shows that the allocentric representations provided by at least some of these cells are very useful for human memory in that where objects and rewards are seen in the world "out there" is a key component of episodic memory and navigation. Spatial view cell representations provide for memory and navigation to be independent of the place where the individual is currently located and of the egocentric coordinates of the viewed location and the facing direction of the individual. Second, memory and navigation in humans are normally related to the visual cues encoded by spatial view cells that define a location "out there" such as a building, hill, and so forth, not to an unmarked place without local cues and identified only by distant environmental/room cues. Third, "mixed" representations, for example of particular combinations of spatial view and place, can arise if the training has been for only some combinations of place and view, for that is what can then be learned by the hippocampus. Fourth, rodents, with their much less good visual acuity (~1 cycle/° in rats, compared with ~60 cycles/° for the human fovea), and rodents' very wide viewing angle for the world (~270°) might be expected, when using the same computational mechanisms as in primates, to use widely spaced environmental cues to define a place where the rodent is located, supported by inputs about place using local olfactory and tactile cues. Fifth, it is shown how view-point dependent allocentric representations could form a view-point independent allocentric representation for memory and navigation. Sixth, concept cells in humans and primates with connectivity to the hippocampus are compared.

The role of the parahippocampal cortex in landmark-based distance estimation based on the contextual hypothesis.

Parahippocampal cortex (PHC) is a vital neural bases in spatial navigation. However, its functional role is still unclear. "Contextual hypothesis," which assumes that the PHC participates in processing the spatial association between the landmark and destination, provides a potential answer to the question. Nevertheless, the hypothesis was previously tested using the picture categorization task, which is indirectly related to spatial navigation. By now, study is still needed for testing the hypothesis with a navigation-related paradigm. In the current study, we tested the hypothesis by an fMRI experiment in which participants performed a distance estimation task in a virtual environment under three different conditions: landmark free (LF), stable landmark (SL), and ambiguous landmark (AL). By analyzing the behavioral data, we found that the presence of an SL improved the participants' performance in distance estimation. Comparing the brain activity in SL-versus-LF contrast as well as AL-versus-LF contrast, we found that the PHC was activated by the SL rather than by AL when encoding the distance. This indicates that the PHC is elicited by strongly associated context and encodes the landmark reference for distance perception. Furthermore, accessing the representational similarity with the activity of the PHC across conditions, we observed a high similarity within the same condition but low similarity between conditions. This result indicated that the PHC sustains the contextual information for discriminating between scenes. Our findings provided insights into the neural correlates of the landmark information processing from the perspective of contextual hypothesis.

Altered Functional Connectivity Strength in Distinct Brain Networks of Children With Early-Onset Schizophrenia.

BACKGROUND: Schizophrenia is regarded as a brain network or connectome disorder that is associated with neurodevelopment. Children with early-onset schizophrenia (EOS) provide an opportunity to evaluate the neuropathology of schizophrenia at a very early stage without potential confounding factors. But dysfunction in brain networks of schizophrenia is inconsistent. PURPOSE: To identify abnormal functional connectivity (FC) in EOS patients and relationships with clinical symptoms, we aimed to reveal neuroimaging phenotypes of EOS. STUDY TYPE: Prospective, cross-sectional. POPULATION: Twenty-six female/22 male patients (age:14.3 ± 3.45 years) with first-episode EOS, 27 female/22 male age- and gender-matched healthy controls (HC) (age:14.1 ± 4.32). FIELD STRENGTH/SEQUENCE: 3-T, resting-state (rs) gradient-echo echo-planar imaging and three-dimensional magnetization-prepared rapid gradient-echo imaging. ASSESSMENT: Intelligence quotient (IQ) was measured by the Wechsler Intelligence Scale-Fourth edition for Children (WISC-IV). The clinical symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS). FC strength (FCS) from rs functional MRI (rsfMRI) was used to investigate functional integrity of global brain regions. In addition, associations between regionally altered FCS and clinical symptoms in EOS patients were examined. STATISTICAL TESTS: Two-sample t-test controlling for sample size, diagnostic method, brain volume algorithm, and age of the subjects, Bonferroni correction, Pearson's correlation analysis. A P-value <0.05 with a minimum cluster size of 50 voxels was considered statistically significant. RESULTS: Compared with HC, EOS patients had significantly lower total IQ scores (IQ:91.5 ± 16.1), increased FCS in the bilateral precuneus, left dorsolateral prefrontal cortex, left thalamus, and left parahippocampus (paraHIP), and decreased FCS in the right cerebellum posterior lobe and right superior temporal gyrus. The PANSS total score of EOS patients (PANSS total score:74.30 ± 7.23) was found to be positively correlated to FCS in the left paraHIP (r = 0.45). DATA CONCLUSION: Our study revealed that disrupted FC of brain hubs illustrate multiple abnormalities in brain networks in EOS patients. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY STAGE: 2.

Impaired Filtering and Hyperfocusing: Neural Evidence for Distinct Selective Attention Abnormalities in People with Schizophrenia.

Although schizophrenia is classically thought to involve impaired attentional filtering, people with schizophrenia (PSZ) exhibit a more intense and more exclusive attentional focus than healthy control subjects (HCS) in many tasks. To resolve this contradiction, this functional magnetic resonance imaging study tested the impact of attentional control demands on the modulation of stimulus-induced activation in the fusiform face area and parahippocampal place area when participants (43 PSZ and 43 HCS) were looking for a target face versus house. Stimuli were presented individually, or as face-house overlays that challenged attentional control. Responses were slower for house than face stimuli and when prioritizing houses over faces in overlays, suggesting a difference in salience. Blood-oxygen-level-dependent activity reflected poorer attentional selectivity in PSZ than HCS when attentional control was challenged most, that is, when stimuli were overlaid and the task required detecting the lower-salience house target. By contrast, attentional selectivity was exaggerated in PSZ when control was challenged least, that is, when stimuli were presented sequentially and the task required detecting the higher-salience face target. These findings are consistent with 2 distinct attentional abnormalities in schizophrenia leading to impaired and exaggerated selection under different conditions: attentional control deficits, and hyperfocusing once attention has been directed toward a stimulus.