Spatial representation of multidimensional information in emotional faces revealed by fMRI.

Face perception is a complex process that involves highly specialized procedures and mechanisms. Investigating into face perception can help us better understand how the brain processes fine-grained, multidimensional information. This research aimed to delve deeply into how different dimensions of facial information are represented in specific brain regions or through inter-regional connections via an implicit face recognition task. To capture the representation of various facial information in the brain, we employed support vector machine decoding, functional connectivity, and model-based representational similarity analysis on fMRI data, resulting in the identification of three crucial findings. Firstly, despite the implicit nature of the task, emotions were still represented in the brain, contrasting with all other facial information. Secondly, the connection between the medial amygdala and the parahippocampal gyrus was found to be essential for the representation of facial emotion in implicit tasks. Thirdly, in implicit tasks, arousal representation occurred in the parahippocampal gyrus, while valence depended on the connection between the primary visual cortex and the parahippocampal gyrus. In conclusion, these findings dissociate the neural mechanisms of emotional valence and arousal, revealing the precise spatial patterns of multidimensional information processing in faces.

Volume of the Dentate Gyrus/CA4 Hippocampal subfield mediates the interplay between sleep quality and depressive symptoms / El volumen del subcampo del giro dentado/hipocampo CA4 media la interacción entre la calidad del sueño y los síntomas depresivos

Background: Emerging evidence increasingly suggests that poor sleep quality is associated with depressive symptoms. The hippocampus might play a crucial role in the interplay between sleep disturbance and depressive symptomatology, e.g., hippocampal atrophy is typically seen in both insomnia disorder and depression. Thus, examining the role of hippocampal volume in the interplay between poor sleep quality and depressive symptoms in large healthy populations is vital. Methods: We investigated the association between self-reported sleep quality, depressive symptoms, and hippocampal total and subfields’ volumes in 1603 healthy young adults from the Behavioral Brain Research Project. Mediation analysis explored the mediating role of hippocampal volumes between sleep quality and depressive symptoms. Results: Self-reported sleep quality and depressive symptoms were positively correlated. In addition, it negatively related to three hippocampal subfields but not total hippocampal volume. In particular, hippocampal subfield DG and CA4 volumes mediated the interrelationship between poor sleep quality and depressive symptoms. Conclusions: Our findings improved the current understanding of the relationship between sleep disturbance, depressive symptomatology, and hippocampal subfields in healthy populations. Considering the crucial role of DG in hippocampal neurogenesis, our results suggest that poor sleep quality may contribute to depression through a reduction of DG volume leading to impaired neurogenesis which is crucial for the regulation of mood.(AU)

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.

Unsupervised classification of brain-wide axons reveals the presubiculum neuronal projection blueprint.

We present a quantitative strategy to identify all projection neuron types from a given region with statistically different patterns of anatomical targeting. We first validate the technique with mouse primary motor cortex layer 6 data, yielding two clusters consistent with cortico-thalamic and intra-telencephalic neurons. We next analyze the presubiculum, a less-explored region, identifying five classes of projecting neurons with unique patterns of divergence, convergence, and specificity. We report several findings: individual classes target multiple subregions along defined functions; all hypothalamic regions are exclusively targeted by the same class also invading midbrain and agranular retrosplenial cortex; Cornu Ammonis receives input from a single class of presubicular axons also projecting to granular retrosplenial cortex; path distances from the presubiculum to the same targets differ significantly between classes, as do the path distances to distinct targets within most classes; the identified classes have highly non-uniform abundances; and presubicular somata are topographically segregated among classes. This study thus demonstrates that statistically distinct projections shed light on the functional organization of their circuit.

What is the role of the hippocampus and parahippocampal gyrus in the persistence of tinnitus?

The hippocampus and parahippocampal gyrus have been implicated as part of a tinnitus network by a number of studies. These structures are usually considered in the context of a "limbic system," a concept typically invoked to explain the emotional response to tinnitus. Despite this common framing, it is not apparent from current literature that this is necessarily the main functional role of these structures in persistent tinnitus. Here, we highlight a different role that encompasses their most commonly implicated functional position within the brain-that is, as a memory system. We consider tinnitus as an auditory object that is held in memory, which may be made persistent by associated activity from the hippocampus and parahippocampal gyrus. Evidence from animal and human studies implicating these structures in tinnitus is reviewed and used as an anchor for this hypothesis. We highlight the potential for the hippocampus/parahippocampal gyrus to facilitate maintenance of the memory of the tinnitus percept via communication with auditory cortex, rather than (or in addition to) mediating emotional responses to this percept.

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.

Pathological neurons generate ripples at the UP-DOWN transition disrupting information transfer.

OBJECTIVE: To confirm and investigate why pathological high-frequency oscillations (pHFOs), including ripples (80-200 Hz) and fast ripples (200-600 Hz), are generated during the UP-DOWN transition of the slow wave and if information transmission mediated by ripple temporal coupling is disrupted in the seizure-onset zone (SOZ). METHODS: We isolated 217 total units from 175.95 intracranial electroencephalography (iEEG) contact-hours of synchronized macro- and microelectrode recordings from 6 patients. Sleep slow oscillation (.1-2 Hz) epochs were identified in the iEEG recording. iEEG HFOs that occurred superimposed on the slow wave were transformed to phasors and adjusted by the phase of maximum firing in nearby units (i.e., maximum UP). We tested whether, in the SOZ, HFOs and associated action potentials (APs) occur more often at the UP-DOWN transition. We also examined ripple temporal correlations using cross-correlograms. RESULTS: At the group level in the SOZ, HFO and HFO-associated AP probability was highest during the UP-DOWN transition of slow wave excitability (p < < .001). In the non-SOZ, HFO and HFO-associated AP was highest during the DOWN-UP transition (p < < .001). At the unit level in the SOZ, 15.6% and 20% of units exhibited more robust firing during ripples (Cohen's d = .11-.83) and fast ripples (d = .36-.90) at the UP-DOWN transition (p < .05 f.d.r. corrected), respectively. By comparison, also in the SOZ, 6.6% (d = .14-.30) and 8.5% (d = .33-.41) of units had significantly less firing during ripples and fast ripples at the UP-DOWN transition, respectively. Additional data shows that ripple and fast ripple temporal correlations, involving global slow waves, between the hippocampus, entorhinal cortex, and parahippocampal gyrus were reduced by >50% in the SOZ compared to the non-SOZ (N = 3). SIGNIFICANCE: The UP-DOWN transition of slow wave excitability facilitates the activation of pathological neurons to generate pHFOs. Ripple temporal correlations across brain regions may be important in memory consolidation and are disrupted in the SOZ, perhaps by pHFO generation.

The functional connectivity between right parahippocampal gyrus and precuneus underlying the association between reward sensitivity and procrastination.

Procrastination has adverse effects on personal growth and social development. Behavior research has found reward sensitivity is positively correlated with procrastination. However, it remains unclear that the neural substrates underlie the relationship between reward sensitivity and procrastination. To address this issue, the present study used voxel-based morphometry (VBM) and resting-state functional connectivity (RSFC) analyses to investigate the neural substrates underlying the association with reward sensitivity and procrastination in two independent samples (N1 = 388, N2 = 330). In Sample 1, the behavioral result indicated reward sensitivity was positively correlated with procrastination. Moreover, the VBM analysis showed that reward sensitivity was positively associated with the gray matter volume (GMV) of the right parahippocampal gyrus. Furthermore, the RSFC result found reward sensitivity was negatively associated with the functional connectivity of the right parahippocampal gyrus-precuneus. Crucially, the mediation analysis revealed that functional connectivity of the right parahippocampal gyrus-precuneus mediated the relationship between reward sensitivity and procrastination. To verify the robustness of the results, confirmatory analysis was carried out in Sample 2. The results of Sample 1 (i.e., the behavioral, VBM, RSFC, and mediation results) can be verified in Sample 2. In brief, these findings suggested that the functional connectivity of the right parahippocampal gyrus-precuneus involved in reward impulsive control could modulate the relationship between reward sensitivity and procrastination, which is the first to reveal the neural underpinning of the association between reward sensitivity and procrastination.

Minute-scale oscillatory sequences in medial entorhinal cortex.

The medial entorhinal cortex (MEC) hosts many of the brain's circuit elements for spatial navigation and episodic memory, operations that require neural activity to be organized across long durations of experience1. Whereas location is known to be encoded by spatially tuned cell types in this brain region2,3, little is known about how the activity of entorhinal cells is tied together over time at behaviourally relevant time scales, in the second-to-minute regime. Here we show that MEC neuronal activity has the capacity to be organized into ultraslow oscillations, with periods ranging from tens of seconds to minutes. During these oscillations, the activity is further organized into periodic sequences. Oscillatory sequences manifested while mice ran at free pace on a rotating wheel in darkness, with no change in location or running direction and no scheduled rewards. The sequences involved nearly the entire cell population, and transcended epochs of immobility. Similar sequences were not observed in neighbouring parasubiculum or in visual cortex. Ultraslow oscillatory sequences in MEC may have the potential to couple neurons and circuits across extended time scales and serve as a template for new sequence formation during navigation and episodic memory formation.

Hierarchical organization of the human ventral visual streams revealed with magnetoencephalography.

The hierarchical organization between 25 ventral stream visual cortical regions and 180 cortical regions was measured with magnetoencephalography using the Human Connectome Project Multimodal Parcellation atlas in 83 Human Connectome Project participants performing a visual memory task. The aim was to reveal the hierarchical organization using a whole-brain model based on generative effective connectivity with this fast neuroimaging method. V1-V4 formed a first group of interconnected regions. Especially V4 had connectivity to a ventrolateral visual stream: V8, the fusiform face cortex, and posterior inferior temporal cortex PIT. These regions in turn had effectivity connectivity to inferior temporal cortex visual regions TE2p and TE1p. TE2p and TE1p then have connectivity to anterior temporal lobe regions TE1a, TE1m, TE2a, and TGv, which are multimodal. In a ventromedial visual stream, V1-V4 connect to ventromedial regions VMV1-3 and VVC. VMV1-3 and VVC connect to the medial parahippocampal gyrus PHA1-3, which, with the VMV regions, include the parahippocampal scene area. The medial parahippocampal PHA1-3 regions have connectivity to the hippocampal system regions the perirhinal cortex, entorhinal cortex, and hippocampus. These effective connectivities of two ventral visual cortical streams measured with magnetoencephalography provide support to the hierarchical organization of brain systems measured with fMRI, and new evidence on directionality.

Multi-omic atlas of the parahippocampal gyrus in Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of dementia worldwide, with a projection of 151 million cases by 2050. Previous genetic studies have identified three main genes associated with early-onset familial Alzheimer's disease, however this subtype accounts for less than 5% of total cases. Next-generation sequencing has been well established and holds great promise to assist in the development of novel therapeutics as well as biomarkers to prevent or slow the progression of this devastating disease. Here we present a public resource of functional genomic data from the parahippocampal gyrus of 201 postmortem control, mild cognitively impaired (MCI) and AD individuals from the Mount Sinai brain bank, of which whole-genome sequencing (WGS), and bulk RNA sequencing (RNA-seq) were previously published. The genomic data include bulk proteomics and DNA methylation, as well as cell-type-specific RNA-seq and assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) data. We have performed extensive preprocessing and quality control, allowing the research community to access and utilize this public resource available on the Synapse platform at https://doi.org/10.7303/syn51180043.2 .

Immediate visual reproduction negatively correlates with brain entropy of parahippocampal gyrus and inferior occipital gyrus in bipolar II disorder adolescents.

BACKGROUND: Brain entropy reveals complexity and irregularity of brain, and it has been proven to reflect brain complexity alteration in disease states. Previous studies found that bipolar disorder adolescents showed cognitive impairment. The relationship between complexity of brain neural activity and cognition of bipolar II disorder (BD-II) adolescents remains unclear. METHODS: Nineteen BD-II patients (14.63 ±1.57 years old) and seventeen age-gender matched healthy controls (HCs) (14.18 ± 1.51 years old) were enlisted. Entropy values of all voxels of the brain in resting-state functional MRI data were calculated and differences of them between BD-II and HC groups were evaluated. After that, correlation analyses were performed between entropy values of brain regions showing significant entropy differences and clinical indices in BD-II adolescents. RESULTS: Significant differences were found in scores of immediate visual reproduction subtest (VR-I, p = 0.003) and Stroop color-word test (SCWT-1, p = 0.015; SCWT-2, p = 0.004; SCWT-3, p = 0.003) between the two groups. Compared with HCs, BD-II adolescents showed significant increased brain entropy in right parahippocampal gyrus and right inferior occipital gyrus. Besides, significant negative correlations between brain entropy values of right parahippocampal gyrus, right inferior occipital gyrus and immediate visual reproduction subtest scores were observed in BD-II adolescents. CONCLUSIONS: The findings of the present study suggested that the disrupted function of corticolimbic system is related with cognitive abnormality of BD-II adolescents. And from the perspective temporal dynamics of brain system, the current study, brain entropy may provide available evidences for understanding the underlying neural mechanism in BD-II adolescents.

Using image reconstruction to investigate face perception in amnesia.

Damage to the medial temporal lobe (MTL), which is traditionally considered to subserve memory exclusively, has been reported to contribute to impaired face perception. However, it remains unknown how exactly such brain lesions may impact face representations and in particular facial shape and surface information, both of which are crucial for face perception. The present study employed a behavioral-based image reconstruction approach to reveal the pictorial representations of face perception in two amnesic patients: DA, who has an extensive bilateral MTL lesion that extends beyond the MTL in the right hemisphere, and BL, who has damage to the hippocampal dentate gyrus (DG). Both patients and their respective matched controls completed similarity judgments for pairs of faces, from which facial shape and surface features were subsequently derived and synthesized to create images of reconstructed facial appearance. Participants also completed a face oddity judgment task (FOJT) that has previously been shown to be sensitive to MTL cortical damage. While BL exhibited an impaired pattern of performance on the FOJT, DA demonstrated intact performance accuracy. Notably, the recovered pictorial content of faces was comparable between both patients and controls, although there was evidence for atypical face representations in BL particularly with regards to color. Our work provides novel insight into the face representations underlying face perception in two well-studied amnesic patients in the literature and demonstrates the applicability of the image reconstruction approach to individuals with brain damage.

Larger left hippocampal presubiculum is associated with lower risk of antisocial behavior in healthy adults with childhood conduct history.

Conduct Disorder (CD) is defined as aggressive, antisocial, and rule-breaking behavior during childhood. It is a major risk factor for developing antisocial personality disorder (ASPD) in adulthood. However, nearly half the CDs do not develop ASPD. Identification of reversion factors seems crucial for proper interventions. We identified 40 subjects with childhood history of CD (CC) and 1166 control subjects (HC) from Human Connectome Project. Their psychiatric, emotional, impulsivity, and personality traits were extracted. An emotion recognition task-fMRI analysis was done. We also did subregion analysis of hippocampus and amygdala in 35 CC and 69 demographically matched HCs. CC subjects scored significantly higher in antisocial-related evaluations. No differences in task-fMRI activation of amygdala and hippocampus were observed. CCs had larger subfields of the left hippocampus: presubiculum, CA3, CA4, and dentate gyrus. Further, an interaction model revealed a significant presubiculum volume × group association with antisocial, aggression, and agreeableness scores. Our study shows that healthy young adults with a prior history of CD still exhibit some forms of antisocial-like behavior with larger left hippocampal subfields, including presubiculum that also explains the variability in antisocial behavior. These larger left hippocampal subfield volumes may play a protective role against CD to ASPD conversion.

Presubiculum principal cells are preserved from degeneration in knock-in APP/TAU mouse models of Alzheimer's disease.

The presubiculum (PRS) is an integral component of the perforant pathway that has recently been recognised as a relatively unscathed region in clinical Alzheimer's disease (AD), despite neighbouring components of the perforant pathway, CA1 and the entorhinal cortex, responsible for formation of episodic memory and storage, showing severe hallmarks of AD including, amyloid-beta (Aß) plaques, tau tangles and marked gliosis. However, the question remains whether this anatomical resilience translates into functional resilience of the PRS neurons. Using neuroanatomy combined with whole-cell electrophysiological recordings, we investigated whether the unique spatial profile of the PRS was replicable in two knock-in mouse models of AD, APPNL-F/NL-F, and APPNL-F/MAPTHTAU and whether the intrinsic properties and morphological integrity of the PRS principal neurons was maintained compared to the lateral entorhinal cortex (LEC) and hippocampal CA1 principal cells. Our data revealed an age-dependent Aß and tau pathology with neuroinflammation in the LEC and CA1, but a presence of fleece-like Aß deposits with an absence of tau tangles and cellular markers of gliosis in the PRS of the mouse models at 11-16 and 18-22 months. These observations were consistent in human post-mortem AD tissue. This spatial profile also correlated with functional resilience of strong burst firing PRS pyramidal cells that showed unaltered sub- and suprathreshold intrinsic biophysical membrane properties and gross morphology in the AD models that were similar to the properties of pyramidal cells recorded in age-matched wild-type mice (11-14 months). This was in contrast to the LEC and CA1 principal cells which showed altered subthreshold intrinsic properties such as a higher input resistance, longer membrane time constants and hyperexcitability in response to suprathreshold stimulation that correlated with atrophied dendrites in both AD models. In conclusion, our data show for the first time that the unique anatomical profile of the PRS constitutes a diffuse AD pathology that is correlated with the preservation of principal pyramidal cell intrinsic biophysical and morphological properties despite alteration of LEC and CA1 pyramidal cells in two distinct genetic models of AD. Understanding the underlying mechanisms of this resilience could be beneficial in preventing the spread of disease pathology before cognitive deficits are precipitated in AD.

Functional lateralization of the medial temporal lobe in novel associative processing during creativity evaluation.

Although hemispheric lateralization of creativity has been a longstanding topic of debate, the underlying neurocognitive mechanism remains poorly understood. Here we designed 2 types of novel stimuli-"novel useful and novel useless," adapted from "familiar useful" designs taken from daily life-to demonstrate how the left and right medial temporal lobe (MTL) respond to novel designs of different usefulness. Taking the "familiar useful" design as a baseline, we found that the right MTL showed increased activation in response to "novel useful" designs, followed by "novel useless" ones, while the left MTL only showed increased activation in response to "novel useful" designs. Calculating an asymmetry index suggests that usefulness processing is predominant in the left MTL, whereas the right MTL is predominantly involved in novelty processing. Moreover, the left parahippocampal gyrus (PHG) showed stronger functional connectivity with the anterior cingulate cortex when responding to "novel useless" designs. In contrast, the right PHG showed stronger connectivity with the amygdala, midbrain, and hippocampus. Critically, multivoxel representational similarity analyses revealed that the left MTL was more effective than the right MTL at distinguishing the usefulness differences in novel stimuli, while representational patterns in the left PHG positively predicted the post-behavior evaluation of "truly creative" products. These findings suggest an apparent dissociation of the left and right MTL in integrating the novelty and usefulness information and novel associative processing during creativity evaluation, respectively. Our results provide novel insights into a longstanding and controversial question in creativity research by demonstrating functional lateralization of the MTL in processing novel associations.

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.

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.

Fan cells in lateral entorhinal cortex directly influence medial entorhinal cortex through synaptic connections in layer 1.

Standard models for spatial and episodic memory suggest that the lateral entorhinal cortex (LEC) and medial entorhinal cortex (MEC) send parallel independent inputs to the hippocampus, each carrying different types of information. Here, we evaluate the possibility that information is integrated between divisions of the entorhinal cortex prior to reaching the hippocampus. We demonstrate that, in mice, fan cells in layer 2 (L2) of LEC that receive neocortical inputs, and that project to the hippocampal dentate gyrus, also send axon collaterals to layer 1 (L1) of the MEC. Activation of inputs from fan cells evokes monosynaptic glutamatergic excitation of stellate and pyramidal cells in L2 of the MEC, typically followed by inhibition that contains fast and slow components mediated by GABAA and GABAB receptors, respectively. Inputs from fan cells also directly activate interneurons in L1 and L2 of MEC, with synaptic connections from L1 interneurons accounting for slow feedforward inhibition of L2 principal cell populations. The relative strength of excitation and inhibition following fan cell activation differs substantially between neurons and is largely independent of anatomical location. Our results demonstrate that the LEC, in addition to directly influencing the hippocampus, can activate or inhibit major hippocampal inputs arising from the MEC. Thus, local circuits in the superficial MEC may combine spatial information with sensory and higher order signals from the LEC, providing a substrate for integration of 'what' and 'where' components of episodic memories.

Hippocampal volume in patients with bilateral and unilateral peripheral vestibular dysfunction.

Previous studies have found that peripheral vestibular dysfunction is associated with altered volumes in different brain structures, especially in the hippocampus. However, published evidence is conflicting. Based on previous findings, we compared hippocampal volume, as well as supramarginal, superior temporal, and postcentral gyrus in a sample of 55 patients with different conditions of peripheral vestibular dysfunction (bilateral, chronic unilateral, acute unilateral) to 39 age- and sex-matched healthy controls. In addition, we explored deviations in gray-matter volumes in hippocampal subfields. We also analysed correlations between morphometric data and visuo-spatial performance. Patients with vestibular dysfunction did not differ in total hippocampal volume from healthy controls. However, a reduced volume in the right presubiculum of the hippocampus and the left supramarginal gyrus was observed in patients with chronic and acute unilateral vestibular dysfunction, but not in patients with bilateral vestibular dysfunction. No association of altered volumes with visuo-spatial performance was found. An asymmetric vestibular input due to unilateral vestibular dysfunction might lead to reduced central brain volumes that are involved in vestibular processing.