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Repetitive transcranial magnetic stimulation (rTMS) of the inferior parietal cortex (IPC) increases resting-state functional connectivity (rsFC) of the hippocampus with the precuneus and other posterior cortical areas and causes proportional improvement of episodic memory. The anatomical pathway(s) responsible for the propagation of these effects from the IPC is unknown and may not be direct. In order to assess the relative contributions of candidate pathways from the IPC to the MTL via the parahippocampal cortex and precuneus, to the effects of rTMS on rsFC and memory improvement, we used diffusion tensor imaging to measure the extent to which individual differences in fractional anisotropy (FA) in these pathways accounted for individual differences in response. FA in the IPC-parahippocampal pathway and several MTL pathways predicted changes in rsFC. FA in both parahippocampal and hippocampal pathways was related to changes in episodic, but not procedural, memory. These results implicate pathways to the MTL in the enhancing effect of parietal rTMS on hippocampal rsFC and memory., (Published by Elsevier Inc.)

Background: The parahippocampal gyrus is understood to have a role in high cognitive functions including memory encoding and retrieval and visuospatial processing. A detailed understanding of the exact location and nature of associated white tracts could significantly improve postoperative morbidity related to declining capacity. Through diffusion tensor imaging-based fiber tracking validated by gross anatomic dissection as ground truth, we have characterized these connections based on relationships to other well-known structures., Methods: Diffusion imaging from the Human Connectome Project for 10 healthy adult controls was used for tractography analysis. We evaluated the parahippocampal gyrus as a whole based on connectivity with other regions. All parahippocampal gyrus tracts were mapped in both hemispheres, and a lateralization index was calculated with resultant tract volumes., Results: We identified 2 connections of the parahippocampal gyrus: inferior longitudinal fasciculus and cingulum. Lateralization of the cingulum was detected (P < 0.05)., Conclusions: The parahippocampal gyrus is an important center for memory processing. Subtle differences in executive functioning following surgery for limbic tumors may be better understood in the context of the fiber-bundle anatomy highlighted by this study., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The hippocampal formation (HPF) is a focus of intense experimental investigation, particularly because of its roles in conscious memory consolidation, spatial navigation, emotion, and motivated behaviors. However, the HPF has a complex three-dimensional geometry resulting from extreme curvature of its layers, and this presents a challenge for investigators seeking to decipher hippocampal structure and function at cellular and molecular scales (neuronal circuitry, gene expression, and other properties). Previously, this problem was solved qualitatively for the rat by constructing a physical surface model of the HPF based on histological sections, and then deriving from the model a flatmap. Its usefulness is exemplified by previous studies that used it to display topological relationships between different components of intrahippocampal circuitry derived from experimental pathway-tracing experiments. Here the rat HPF flatmap was used as a starting point to construct an analogous flatmap for the mouse, where the great majority of experimental hippocampal research is currently performed. A detailed account of underlying knowledge and principles is provided, including for hippocampal terminology, and development from an embryonic nonfolded sheet into differentiated multiple adjacent cortical areas, giving rise to the adult shape. To demonstrate its utility, the mouse flatmap was used to display the results of pathway-tracing experiments showing the dentate gyrus mossy fiber projection, and its relationship to the intrahippocampal Purkinje cell protein 4 gene-expression pattern. Finally, requirements for constructing a computer graphics quantitative intrahippocampal flatmap, with accompanying intrahippocampal coordinate system, are presented; they should be applicable to all mammals, including human., Competing Interests: The authors declare no competing interest.

Humans are remarkably adept at perceiving and understanding complex real-world scenes. Uncovering the neural basis of this ability is an important goal of vision science. Neuroimaging studies have identified three cortical regions that respond selectively to scenes: parahippocampal place area, retrosplenial complex/medial place area, and occipital place area. Here, we review what is known about the visual and functional properties of these brain areas. Scene-selective regions exhibit retinotopic properties and sensitivity to low-level visual features that are characteristic of scenes. They also mediate higher-level representations of layout, objects, and surface properties that allow individual scenes to be recognized and their spatial structure ascertained. Challenges for the future include developing computational models of information processing in scene regions, investigating how these regions support scene perception under ecologically realistic conditions, and understanding how they operate in the context of larger brain networks.

The rat hippocampal formation (HF), parahippocampal region (PHR), and retrosplenial cortex (RSC) play critical roles in spatial processing. These regions are interconnected, and functionally dependent. The neuronal networks mediating this reciprocal dependency are largely unknown. Establishing the developmental timing of network formation will help to understand the emergence of this dependency. We questioned whether the long-range outputs from HF-PHR to RSC in Long Evans rats develop during the same time periods as previously reported for the intrinsic HF-PHR connectivity and the projections from RSC to HF-PHR. The results of a series of retrograde and anterograde tracing experiments in rats of different postnatal ages show that the postnatal projections from HF-PHR to RSC display low densities around birth, but develop during the first postnatal week, reaching adult-like densities around the time of eye-opening. Developing projections display a topographical organization similar to adult projections. We conclude that the long-range projections from HF-PHR to RSC develop in parallel with the intrinsic circuitry of HF-PHR and the projections of RSC to HF-PHR., (© 2019 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

The lateral portion of the entorhinal cortex is one of the first brain regions affected by tau pathology, an important biomarker for Alzheimer disease. Improving our understanding of this region's cognitive role may help identify better cognitive tests for early detection of Alzheimer disease. Based on its functional connections, we tested the idea that the human anterolateral entorhinal cortex (alERC) may play a role in integrating spatial information into object representations. We recently demonstrated that the volume of the alERC was related to processing the spatial relationships of the features within an object [Yeung, L. K., Olsen, R. K., Bild-Enkin, H. E. P., D'Angelo, M. C., Kacollja, A., McQuiggan, D. A., et al. Anterolateral entorhinal cortex volume predicted by altered intra-item configural processing. Journal of Neuroscience, 37, 5527-5538, 2017]. In this study, we investigated whether the human alERC might also play a role in processing the spatial relationships between an object and its environment using an eye-tracking task that assessed visual fixations to a critical object within a scene. Guided by rodent work, we measured both object-in-place memory, the association of an object with a given context [Wilson, D. I., Langston, R. F., Schlesiger, M. I., Wagner, M., Watanabe, S., & Ainge, J. A. Lateral entorhinal cortex is critical for novel object-context recognition. Hippocampus, 23, 352-366, 2013], and object-trace memory, the memory for the former location of objects [Tsao, A., Moser, M. B., & Moser, E. I. Traces of experience in the lateral entorhinal cortex. Current Biology, 23, 399-405, 2013]. In a group of older adults with varying stages of brain atrophy and cognitive decline, we found that the volume of the alERC and the volume of the parahippocampal cortex selectively predicted object-in-place memory, but not object-trace memory. These results provide support for the notion that the alERC may integrate spatial information into object representations.

Orientation in space is a fundamental cognitive process relying on brain-wide neuronal circuits. Many neurons in the presubiculum in the parahippocampal region encode head direction and each head direction cell selectively discharges when the animal faces a specific direction. Here, we attempt to link the current knowledge of afferent and efferent connectivity of the presubiculum to the processing of the head direction signal. We describe the cytoarchitecture of the presubicular six-layered cortex and the morphological and electrophysiological intrinsic properties of principal neurons and interneurons. While the presubicular head direction signal depends on synaptic input from thalamus, the intra- and interlaminar information flow in the microcircuit of the presubiculum may contribute to refine directional tuning. The interaction of a specific interneuron type, the Martinotti cells, with the excitatory pyramidal cells may maintain the head direction signal in the presubiculum with attractor-like properties.

The parahippocampal place area (PPA) is a widely studied high-level visual region in the human brain involved in place and scene processing. The goal of the present study was to identify the most probable location of place-selective voxels in medial ventral temporal cortex. To achieve this goal, we first used cortex-based alignment (CBA) to create a probabilistic place-selective region of interest (ROI) from one group of 12 participants. We then tested how well this ROI could predict place selectivity in each hemisphere within a new group of 12 participants. Our results reveal that a probabilistic ROI (pROI) generated from one group of 12 participants accurately predicts the location and functional selectivity in individual brains from a new group of 12 participants, despite between subject variability in the exact location of place-selective voxels relative to the folding of parahippocampal cortex. Additionally, the prediction accuracy of our pROI is significantly higher than that achieved by volume-based Talairach alignment. Comparing the location of the pROI of the PPA relative to published data from over 500 participants, including data from the Human Connectome Project, shows a striking convergence of the predicted location of the PPA and the cortical location of voxels exhibiting the highest place selectivity across studies using various methods and stimuli. Specifically, the most predictive anatomical location of voxels exhibiting the highest place selectivity in medial ventral temporal cortex is the junction of the collateral and anterior lingual sulci. Methodologically, we make this pROI freely available (vpnl.stanford.edu/PlaceSelectivity), which provides a means to accurately identify a functional region from anatomical MRI data when fMRI data are not available (for example, in patient populations). Theoretically, we consider different anatomical and functional factors that may contribute to the consistent anatomical location of place selectivity relative to the folding of high-level visual cortex., (Copyright © 2017 Elsevier Inc. All rights reserved.)

What has been long absent in understanding the neural circuit that supports spatial processing is a thorough description and rigorous study of the distributed neural networks associated with spatial processing-both in the human as well as in rodents. Most of our understanding regarding the elucidation of a spatial neural circuit has been based on rodents and therefore the present manuscript will concentrate on that literature. There is a trend emerging in research to expand beyond the hippocampus for evaluating spatial memory, but the thrust of the research still focuses on the role of the hippocampus as essential and other neural substrates as performing sub-servient roles to support hippocampus-dependent spatial processing. This review will describe spatial memory in terms of a system model incorporating partially overlapping and interacting event-based, knowledge-based and rule-based memory systems that are composed of different component processes or attributes associated with spatial processing which are mapped onto the corresponding neural substrates and larger networks. In particular, the interactions among brain systems that process spatial information will be emphasized. We propose that these interactions among brain regions are essential for spatial memory., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The laminar and topographical organization of connections between the hippocampal formation and parahippocampal regions was investigated in the rabbit following in vivo injection of cholera toxin B subunit as a retro- and antero-grade tracer and biotinylated dextran amine as an anterograde tracer. We confirmed several connectional features different from those of the rat, that is, the rabbit presubiculum received abundant afferents from CA1 and had many reciprocal connections with the entorhinal cortex. On the other hand, we identified many similarities with the rat: both the CA1 and subicular afferents that originated from the entorhinal cortex were abundant; moreover, the presubiculum received many inputs from the subiculum and sent massive projections to the entorhinal cortex. By plotting retrograde and anterograde labels in two-dimensional unfolded maps of the entire hippocampal and parahippocampal regions, we found that each group of entorhinal cells that project to CA1, subiculum, and presubiculum, and also the termination of the presubiculo-entorhinal projection, was distributed in band-like zones in layers II-III, extending across the medial and lateral entorhinal cortex. Our results suggest that the rabbit has a basic connectivity that is common with that of the rat, and also has additional hippocampal-presubicular and entorhino-presubicular connections that may reflect functional evolution in learning and memory., (© 2017 Wiley Periodicals, Inc.)

The relationship between the local morphological features that define the entorhinal and parahippocampal cortex in the medial temporal region of the human brain and activation as measured during a navigation task with functional magnetic resonance imaging was examined individually in healthy participants. Two functional activation clusters were identified one within the caudal end of the collateral sulcus proper and the other in the parahippocampal extension of the collateral sulcus, clearly establishing the activation in the posterior parahippocampal cortex. A third activation cluster was identified where the anterior segment of the collateral sulcus proper gives way to the posterior segment, demonstrating also activation within the middle parahippocampal cortex. No activation was observed in the entorhinal cortex that lies medial to the rhinal sulcus or in the anterior part of the parahippocampal cortex along the anterior branch of the collateral sulcus proper. The activations could also be clearly differentiated from the cortex of the fusiform and lingual gyri that lie laterally and posteriorly. These findings demonstrated specific activation in the middle and posterior part of the parahippocampal cortex when information necessary for navigation was retrieved from a previously established cognitive map and demonstrate that the sulci that comprise the collateral sulcal complex represent important landmarks that can provide an accurate localization of activation foci along the parahippocampal cortex and allow identification of subdivisions involved in the processing of spatial information.

Anatomical and functional findings in primates suggest the existence of a dedicated parieto-medial temporal pathway for spatial navigation, consisting of both direct and indirect projections from the caudal inferior parietal lobe (cIPL) to the hippocampus and the parahippocampal cortex, with indirect projections relaying through the posterior cingulate and retrosplenial cortex. This neural network is largely unexplored in humans. This study aimed at testing the existence of a parieto-medial temporal pathway for spatial navigation in humans. We explored the cortical connectivity patterns of the parahippocampal place area (PPA), the retrosplenial cortex (RSC), and the hippocampus (HC) using resting-state functional connectivity MRI. Our results demonstrate the existence of connections between the medial temporal lobe structures, i.e., PPA and HC, and the angular gyrus (AG), the human homologue of cIPL, as well as between RSC and AG. These connectivity patterns seem to reflect the direct and the indirect projections found in primates from cIPL to the medial temporal lobe. Such a result deserves feasible considerations to better understand the brain networks underpinning human spatial navigation.

Recent evidence suggests that individual differences in physical activity (PA) may be associated with individual differences in white matter microstructure and with grey matter volume of the hippocampus. Therefore, this study investigated the association between PA and white matter microstructure of pathways connecting to the hippocampus. A total of 33 young, healthy adults underwent magnetic resonance imaging (MRI). High angular resolution diffusion-weighted imaging and multi-component relaxometry MRI scans (multi-component driven equilibrium pulse observation of T1 and T2) were acquired for each participant. Activity levels (AL) of participants were calculated from 72-h actigraphy recordings. Tractography using the damped Richardson Lucy algorithm was used to reconstruct the fornix and bilateral parahippocampal cinguli (PHC). The mean fractional anisotropy (FA) and the myelin water fraction (MWF), a putative marker of myelination, were determined for each pathway. A positive correlation between both AL and FA and between AL and MWF were hypothesized for the three pathways. There was a selective positive correlation between AL and MWF in the right PHC (r = 0.482, p = 0.007). Thus, our results provide initial in vivo evidence for an association between myelination of the right PHC and PA in young healthy adults. Our results suggest that MWF may not only be more specific, but also more sensitive than FA to detect white matter microstructural alterations. If PA was to induce structural plasticity of the right PHC this may contribute to reverse structural alterations of the right PHC in neuropsychiatric disorder with hippocampal pathologies.

There is a keen interest in identifying specific brain regions that are related to individual differences in true and false memories. Previous functional neuroimaging studies showed that activities in the hippocampus, right fusiform gyrus, and parahippocampal gyrus were associated with true and false memories, but no study thus far has examined whether the structures of these brain regions are associated with short-term and long-term true and false memories. To address that question, the current study analyzed data from 205 healthy young adults, who had valid data from both structural brain imaging and a misinformation task. In the misinformation task, subjects saw the crime scenarios, received misinformation, and took memory tests about the crimes an hour later and again after 1.5 years. Results showed that bilateral hippocampal volume was associated with short-term true and false memories, whereas right fusiform gyrus volume and surface area were associated with long-term true and false memories. This study provides the first evidence for the structural neural bases of individual differences in short-term and long-term true and false memories.

The sulcal segments of the collateral sulcal complex on the medial part of the temporal lobe delineate the parahippocampal gyrus involved in memory processing from the laterally adjacent fusiform gyrus. The rhinal sulcus delineates the entorhinal cortex on the anterior portion of the parahippocampal gyrus. Posterior to the rhinal sulcus lies the collateral sulcus proper which delineates the parahippocampal cortex that occupies the posterior part of the parahippocampal gyrus. A small sulcus, the parahippocampal extension of the collateral sulcus, runs transversely within the parahippocampal gyrus. The rhinal sulcus, the collateral sulcus proper, and the parahippocampal extension of the collateral sulcus were identified on magnetic resonance images of 40 healthy human brains and probability maps were created to provide quantification of the location variability within standard stereotaxic space. These probability maps can act as a reference frame for the accurate identification of key components of the parahippocampal region and assist in the interpretation of structural and functional changes obtained in neuroimaging studies.

Covering the heads of human volunteers with a toque lined with copper mesh compared to no mesh resulted in significant diminishments in quantitative electroencephalographic power within theta and beta-gamma bands over the right caudal hemisphere. The effect was most evident in women compared to men. The significant attenuation of power was verified by LORETA (low resolution electromagnetic tomography) within the parahippocampal region of the right hemisphere. Direct measurements of frequency-dependent voltages of coronal section preserved in ethanol-formalin-acetic acid from our human brain collection revealed consistently elevated power (0.2μV(2)Hz(-1)) in right hemispheric structures compared to left. The discrepancy was most pronounced in the grey (cortical) matter of the right parahippocampal region. Probing the superficial convexities of the cerebrum in an unsectioned human brain demonstrated rostrocaudal differences in hemispheric spectral power density asymmetries, particularly over caudal and parahippocampal regions, which were altered as a function of the chemical and spatial contexts imposed upon the tissue. These results indicate that the heterogeneous response of the human cerebrum to covering of the head by a thin conductor could reflect an intrinsic structure and unique electrical property of the (entorhinal) cortices of the right caudal hemisphere that persists in fixed tissue., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Neurons coding for head-direction are crucial for spatial navigation. Here we explored the cellular basis of head-direction coding in the rat dorsal presubiculum (PreS). We found that layer2 is composed of two principal cell populations (calbindin-positive and calbindin-negative neurons) which targeted the contralateral PreS and retrosplenial cortex, respectively. Layer3 pyramidal neurons projected to the medial entorhinal cortex (MEC). By juxtacellularly recording PreS neurons in awake rats during passive-rotation, we found that head-direction responses were preferentially contributed by layer3 pyramidal cells, whose long-range axons branched within layer3 of the MEC. In contrast, layer2 neurons displayed distinct spike-shapes, were not modulated by head-direction but rhythmically-entrained by theta-oscillations. Fast-spiking interneurons showed only weak directionality and theta-rhythmicity, but were significantly modulated by angular velocity. Our data thus indicate that PreS neurons differentially contribute to head-direction coding, and point to a cell-type- and layer-specific routing of directional and non-directional information to downstream cortical targets.

Graph theory was used to analyze the anatomical network of the rat hippocampal formation and the parahippocampal region (van Strien et al., Nat Rev Neurosci 10(4):272-282, 2009). For this analysis, the full network was decomposed along the three anatomical axes, resulting in three networks that describe the connectivity within the rostrocaudal, dorsoventral and laminar dimensions. The rostrocaudal network had a connection density of 12% and a path length of 2.4. The dorsoventral network had a high cluster coefficient (0.53), a relatively high path length (1.62) and a rich club was identified. The modularity analysis revealed three modules in the dorsoventral network. The laminar network contained most information. The laminar dimension revealed a network with high clustering coefficient (0.47), a relatively high path length (2.11) and four significantly increased characteristic network building blocks (structural motifs). Thirteen rich club nodes were identified, almost all of them situated in the parahippocampal region. Six connector hubs were detected and all of them were located in the entorhinal cortex. Three large modules were revealed, indicating a close relationship between the perirhinal and postrhinal cortex as well as between the lateral and medial entorhinal cortex. These results confirmed the central position of the entorhinal cortex in the (para)hippocampal network and this possibly explains why pathology in this region has such profound impact on cognitive function, as seen in several brain diseases. The results also have implications for the idea of strict separation of the "spatial" and the "non-spatial" information stream into the hippocampus. This two-stream memory model suggests that the information influx from, respectively, the postrhinal-medial entorhinal cortex and the perirhinal-lateral entorhinal cortex is separate, but the current analysis shows that this apparent separation is not determined by anatomical constraints.

Objective: We used microscopy to conduct qualitative and quantitative analysis of 4 surgical approaches commonly used in the surgery of the ambient cistern: infratentorial supracerebellar (SC), occipital interhemispheric, subtemporal (ST), and transchoroidal (TC). In addition, we performed a parahippocampal gyrus resection in the ST context., Methods: Each approach was performed in 3 cadaveric heads (6 sides). After the microscopic anatomic dissection, the parahippocampal gyrus was resected through an ST approach. The qualitative analysis was based on anatomic observation and the quantitative analysis was based on the linear exposure of vascular structures and the area of exposure of the ambient cistern region., Results: The ST approach provided good exposure of the inferior portion of the cistern and of the proximal segments of the posterior cerebral artery. After the resection of the parahippocampal gyrus, the area of exposure improved in all components, especially the superior area. A TC approach provided the best exposure of the superior area compared with the other approaches. The posterolateral approaches (SC/occipital interhemispheric) to the ambient cistern region provided similar exposure of anatomic structures. There was a significant difference (P < 0.05) in linear exposure of the posterior cerebral artery when comparing the ST/TC and ST/SC approaches., Conclusions: This study has demonstrated that surgical approaches expose dissimilarly the different regions of the ambient cistern and an approach should be selected based on the specific need of anatomic exposure., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Recent years have seen a growing interest in the neuroscience of spontaneous cognition. One form of such cognition is involuntary musical imagery (INMI), the non-pathological and everyday experience of having music in one's head, in the absence of an external stimulus. In this study, aspects of INMI, including frequency and affective evaluation, were measured by self-report in 44 subjects and related to variation in brain structure in these individuals. Frequency of INMI was related to cortical thickness in regions of right frontal and temporal cortices as well as the anterior cingulate and left angular gyrus. Affective aspects of INMI, namely the extent to which subjects wished to suppress INMI or considered them helpful, were related to gray matter volume in right temporopolar and parahippocampal cortices respectively. These results provide the first evidence that INMI is a common internal experience recruiting brain networks involved in perception, emotions, memory and spontaneous thoughts., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Although much attention has been directed towards life satisfaction that refers to an individual's general cognitive evaluations of his or her life as a whole, little is known about the neural basis underlying global life satisfaction. In this study, we used voxel-based morphometry to investigate the structural neural correlates of life satisfaction in a large sample of young healthy adults (n = 299). We showed that individuals' life satisfaction was positively correlated with the regional gray matter volume (rGMV) in the right parahippocampal gyrus (PHG), and negatively correlated with the rGMV in the left precuneus and left ventromedial prefrontal cortex. This pattern of results remained significant even after controlling for the effect of general positive and negative affect, suggesting a unique structural correlates of life satisfaction. Furthermore, we found that self-esteem partially mediated the association between the PHG volume and life satisfaction as well as that between the precuneus volume and global life satisfaction. Taken together, we provide the first evidence for the structural neural basis of life satisfaction, and highlight that self-esteem might play a crucial role in cultivating an individual's life satisfaction., (© The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.)

The insular cortex is involved in the perception of interoceptive signals, coding of emotional and affective states, and processing information from gustatory, olfactory, auditory, somatosensory, and nociceptive modalities. This information represents an important component of episodic memory, mediated by the parahippocampal-hippocampal region. A comprehensive description of insular projections to the latter region is lacking. Previous studies reported that insular projections do not target any of the subdivisions in the hippocampal formation (the dentate gyus, the cornu ammonis [CA] fields 1, 2, and 3 and the subiculum), but, in contrast, target the parahippocampal region (perirhinal, postrhinal, lateral and medial entorhinal cortices, and pre- and parasubiculum). The present study examined the topographical and laminar organization of insular projections to the parahippocampal region in the rat with the use of anterograde tracing. Notably, our results corroborated the absence of hippocampal projections. We further showed that the perirhinal and the lateral entorhinal cortices received extensive projections from the insular cortex, primarily from its agranular areas. With the exception of a weak projection to the postrhinal cortex, projections to the remaining parahippocampal areas were either absent or very sparse. The projections to the lateral entorhinal cortex displayed a preference for the deep layers of its most lateral subdivisions, known also to receive hippocampal inputs. Projections to the perirhinal cortex primarily targeted the superficial layers with a preference for its ventral subdivision, referred to as area 35. Our findings indicate that only processed information, reflecting emotional and affective states, but not primary gustatory and viscerosensory information, has direct access to the parahippocampal-hippocampal system., (© 2015 Wiley Periodicals, Inc.)

Objective: An increasing number of human in vivo magnetic resonance imaging (MRI) studies have focused on examining the structure and function of the subfields of the hippocampal formation (the dentate gyrus, CA fields 1-3, and the subiculum) and subregions of the parahippocampal gyrus (entorhinal, perirhinal, and parahippocampal cortices). The ability to interpret the results of such studies and to relate them to each other would be improved if a common standard existed for labeling hippocampal subfields and parahippocampal subregions. Currently, research groups label different subsets of structures and use different rules, landmarks, and cues to define their anatomical extents. This paper characterizes, both qualitatively and quantitatively, the variability in the existing manual segmentation protocols for labeling hippocampal and parahippocampal substructures in MRI, with the goal of guiding subsequent work on developing a harmonized substructure segmentation protocol., Method: MRI scans of a single healthy adult human subject were acquired both at 3 T and 7 T. Representatives from 21 research groups applied their respective manual segmentation protocols to the MRI modalities of their choice. The resulting set of 21 segmentations was analyzed in a common anatomical space to quantify similarity and identify areas of agreement., Results: The differences between the 21 protocols include the region within which segmentation is performed, the set of anatomical labels used, and the extents of specific anatomical labels. The greatest overall disagreement among the protocols is at the CA1/subiculum boundary, and disagreement across all structures is greatest in the anterior portion of the hippocampal formation relative to the body and tail., Conclusions: The combined examination of the 21 protocols in the same dataset suggests possible strategies towards developing a harmonized subfield segmentation protocol and facilitates comparison between published studies., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Global and regional cortical thicknesses based on T1-weighted magnetic resonance images acquired at 1.5 T and 3 T were measured on a relatively large cohort of 295 subjects using FreeSurfer software. Multivariate regression analysis was performed using Pillai's trace test to determine significant differences in cortical thicknesses measured at these two field strengths. Our results indicate that global cortical thickness is not affected by the field strength or gender. In contrast, the regional cortical thickness was observed to be field dependent. Specifically, the cortical thickness in regions such as parahippocampal, superior temporal, precentral and posterior cingulate is thicker at 3 T than at 1.5 T. In contrast regions such as cuneus and pericalcarine showed higher cortical thickness at 1.5 T than at 3 T. These differences appear to be age-dependent. The differences in regional cortical thickness between field strengths were similar in both genders. Further, male vs. female differences in regional cortical thickness were observed only at 1.5 T and not at 3 T. Our results indicate that magnetic field strength has a significant effect on the estimation of regional, but not global, cortical thickness. In addition, the pulse sequence, scanner type, and spatial resolution do not appear to have significant effect on the measured cortical thickness.

Patients with schizophrenia show widespread cortical thickness reductions throughout the brain. Likewise, reduced expression of the γ-Aminobutyric acid (GABA) synthesizing enzyme glutamic acid decarboxylase (GAD1) and a single nucleotide polymorphism (SNP) rs3749034 in the corresponding gene have been associated with schizophrenia. We tested whether this SNP is associated with reduced cortical thickness, an intermediate phenotype for schizophrenia. Because of the well known interactions between the GABAergic and dopaminergic systems, we examined whether associations between GAD1 rs3749034 and cortical thickness are modulated by the catechol-O-methyltransferase (COMT) Val158Met genotype. Structural MRI and genotype data was obtained from 94 healthy subjects enrolled in the Mind Clinical Imaging Consortium study to examine the relations between GAD1 genotype and cortical thickness. Our data show a robust reduction of cortical thickness in the left parahippocampal gyrus (PHG) in G allele homozygotes of GAD1 rs3749034. When we stratified our analyses according to the COMT Val158Met genotype, cortical thickness reductions of G allele homozygotes were only found in the presence of the Val allele. Genetic risk variants of schizophrenia in the GABAergic system might interact with the dopaminergic system and impact brain structure and functioning. Our findings point to the importance of the GABAergic system in the pathogenesis of schizophrenia., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Previous voxel-based morphometry (VBM) studies have revealed that meditation is associated with structural brain changes in regions underlying cognitive processes that are required for attention or mindfulness during meditation. This VBM study examined brain changes related to the practice of an emotion-oriented meditation: loving-kindness meditation (LKM). A 3 T magnetic resonance imaging (MRI) scanner captured images of the brain structures of 25 men, 10 of whom had practiced LKM in the Theravada tradition for at least 5 years. Compared with novices, more gray matter volume was detected in the right angular and posterior parahippocampal gyri in LKM experts. The right angular gyrus has not been previously reported to have structural differences associated with meditation, and its specific role in mind and cognitive empathy theory suggests the uniqueness of this finding for LKM practice. These regions are important for affective regulation associated with empathic response, anxiety and mood. At the same time, gray matter volume in the left temporal lobe in the LKM experts appeared to be greater, an observation that has also been reported in previous MRI meditation studies on meditation styles other than LKM. Overall, the findings of our study suggest that experience in LKM may influence brain structures associated with affective regulation.

The postrhinal (POR) cortex of the rat is homologous to the parahippocampal cortex of the primate based on connections and other criteria. POR provides the major visual and visuospatial input to the hippocampal formation, both directly to CA1 and indirectly through connections with the medial entorhinal cortex. Although the cortical and hippocampal connections of the POR cortex are well described, the physiology of POR neurons has not been studied. Here, we examined the electrical and morphological characteristics of layer 5 neurons from POR cortex of 14- to 16-day-old rats using an in vitro slice preparation. Neurons were subjectively classified as regular-spiking (RS), fast-spiking (FS), or low-threshold spiking (LTS) based on their electrophysiological properties and similarities with neurons in other regions of neocortex. Cells stained with biocytin included pyramidal cells and interneurons with bitufted or multipolar dendritic patterns. Similarity analysis using only physiological data yielded three clusters that corresponded to FS, LTS, and RS classes. The cluster corresponding to the FS class was composed entirely of multipolar nonpyramidal cells, and the cluster corresponding to the RS class was composed entirely of pyramidal cells. The third cluster, corresponding to the LTS class, was heterogeneous and included both multipolar and bitufted dendritic arbors as well as one pyramidal cell. We did not observe any intrinsically bursting pyramidal cells, which is similar to entorhinal cortex but unlike perirhinal cortex. We conclude that POR includes at least two major classes of neocortical inhibitory interneurons, but has a functionally restricted cohort of pyramidal cells., (Copyright © 2012 Wiley Periodicals, Inc.)

A review of medial temporal lobe connections reveals three distinct groupings of hippocampal efferents. These efferent systems and their putative memory functions are: (1) The 'extended-hippocampal system' for episodic memory, which involves the anterior thalamic nuclei, mammillary bodies and retrosplenial cortex, originates in the subicular cortices, and has a largely laminar organisation; (2) The 'rostral hippocampal system' for affective and social learning, which involves prefrontal cortex, amygdala and nucleus accumbens, has a columnar organisation, and originates from rostral CA1 and subiculum; (3) The 'reciprocal hippocampal-parahippocampal system' for sensory processing and integration, which originates from the length of CA1 and the subiculum, and is characterised by columnar, connections with reciprocal topographies. A fourth system, the 'parahippocampal-prefrontal system' that supports familiarity signalling and retrieval processing, has more widespread prefrontal connections than those of the hippocampus, along with different thalamic inputs. Despite many interactions between these four systems, they may retain different roles in memory which when combined explain the importance of the medial temporal lobe for the formation of declarative memories., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

In this paper, we present two novel perspectives on the function of the left inferior frontal gyrus (LIFG). First, a structured sequence processing perspective facilitates the search for functional segregation within the LIFG and provides a way to express common aspects across cognitive domains including language, music and action. Converging evidence from functional magnetic resonance imaging and transcranial magnetic stimulation studies suggests that the LIFG is engaged in sequential processing in artificial grammar learning, independently of particular stimulus features of the elements (whether letters, syllables or shapes are used to build up sequences). The LIFG has been repeatedly linked to processing of artificial grammars across all different grammars tested, whether they include non-adjacent dependencies or mere adjacent dependencies. Second, we apply the sequence processing perspective to understand how the functional segregation of semantics, syntax and phonology in the LIFG can be integrated in the general organization of the lateral prefrontal cortex (PFC). Recently, it was proposed that the functional organization of the lateral PFC follows a rostro-caudal gradient, such that more abstract processing in cognitive control is subserved by more rostral regions of the lateral PFC. We explore the literature from the viewpoint that functional segregation within the LIFG can be embedded in a general rostro-caudal abstraction gradient in the lateral PFC. If the lateral PFC follows a rostro-caudal abstraction gradient, then this predicts that the LIFG follows the same principles, but this prediction has not yet been tested or explored in the LIFG literature. Integration might provide further insights into the functional architecture of the LIFG and the lateral PFC.

Socioeconomic disparities in childhood are associated with remarkable differences in cognitive and socio-emotional development during a time when dramatic changes are occurring in the brain. Yet, the neurobiological pathways through which socioeconomic status (SES) shapes development remain poorly understood. Behavioral evidence suggests that language, memory, social-emotional processing, and cognitive control exhibit relatively large differences across SES. Here we investigated whether volumetric differences could be observed across SES in several neural regions that support these skills. In a sample of 60 socioeconomically diverse children, highly significant SES differences in regional brain volume were observed in the hippocampus and the amygdala. In addition, SES × age interactions were observed in the left superior temporal gyrus and left inferior frontal gyrus, suggesting increasing SES differences with age in these regions. These results were not explained by differences in gender, race or IQ. Likely mechanisms include differences in the home linguistic environment and exposure to stress, which may serve as targets for intervention at a time of high neural plasticity., (© 2012 Blackwell Publishing Ltd.)

Humans assess the credibility of information gained from others on a daily basis; this ongoing assessment is especially crucial for avoiding exploitation by others. We used a repeated, two-person bargaining game and a cognitive hierarchy model to test how subjects judge the information sent asymmetrically from one player to the other. The weight that they give to this information is the result of two distinct factors: their baseline suspicion given the situation and the suspicion generated by the other person's behavior. We hypothesized that human brains maintain an ongoing estimate of the credibility of the other player and sought to uncover neural correlates of this process. In the game, sellers were forced to infer the value of an object based on signals sent from a prospective buyer. We found that amygdala activity correlated with baseline suspicion, whereas activations in bilateral parahippocampus correlated with trial-by-trial uncertainty induced by the buyer's sequence of suggestions. In addition, the less credible buyers that appeared, the more sensitive parahippocampal activation was to trial-by-trial uncertainty. Although both of these neural structures have previously been implicated in trustworthiness judgments, these results suggest that they have distinct and separable roles that correspond to their theorized roles in learning and memory.

Navigation is mediated by a network of brain areas, and research has focused on the head-direction system in the presubiculum (PrS), the grid cell containing medial entorhinal cortex (EC) (MEC) and place cells in the hippocampus. Less research addressed the interactions of the retrosplenial cortex (RSC) and the navigational system, although it is well established that damage to the RSC leads to navigational deficits. We previously showed that RSC provides a dense input to deep layers of MEC and to superficial layers of PrS. In this study we use confocal microscopical analysis and show that the dense projection from the caudal part of the ventral retrosplenial granular cortex targets neurons in Layer III of PrS, which provide input to superficial layers of MEC. Our high resolution anatomical data indicate that sparsely spiny pyramidal neurons in Layer III of PrS that originate projections to Layer III of MEC are the main target of these retrosplenial projections. Retrosplenial axonal boutons were found to equally contact spines and shafts of basal dendrites in Layer III, but contacts on shafts are more prominent close to the soma, indicating the potential for efficient synaptic transfer. These observations suggest that neurons in Layer III of PrS have an important role in mediating RSC contributions to navigation., (Copyright © 2011 Wiley Periodicals, Inc.)

Findings on song perception and song production have increasingly suggested that common but partially distinct neural networks exist for processing lyrics and melody. However, the neural substrates of song recognition remain to be investigated. The purpose of this study was to examine the neural substrates involved in the accessing "song lexicon" as corresponding to a representational system that might provide links between the musical and phonological lexicons using positron emission tomography (PET). We exposed participants to auditory stimuli consisting of familiar and unfamiliar songs presented in three ways: sung lyrics (song), sung lyrics on a single pitch (lyrics), and the sung syllable 'la' on original pitches (melody). The auditory stimuli were designed to have equivalent familiarity to participants, and they were recorded at exactly the same tempo. Eleven right-handed nonmusicians participated in four conditions: three familiarity decision tasks using song, lyrics, and melody and a sound type decision task (control) that was designed to engage perceptual and prelexical processing but not lexical processing. The contrasts (familiarity decision tasks versus control) showed no common areas of activation between lyrics and melody. This result indicates that essentially separate neural networks exist in semantic memory for the verbal and melodic processing of familiar songs. Verbal lexical processing recruited the left fusiform gyrus and the left inferior occipital gyrus, whereas melodic lexical processing engaged the right middle temporal sulcus and the bilateral temporo-occipital cortices. Moreover, we found that song specifically activated the left posterior inferior temporal cortex, which may serve as an interface between verbal and musical representations in order to facilitate song recognition.

Humans are remarkably efficient at categorizing natural scenes. In fact, scene categories can be decoded from functional MRI (fMRI) data throughout the ventral visual cortex, including the primary visual cortex, the parahippocampal place area (PPA), and the retrosplenial cortex (RSC). Here we ask whether, and where, we can still decode scene category if we reduce the scenes to mere lines. We collected fMRI data while participants viewed photographs and line drawings of beaches, city streets, forests, highways, mountains, and offices. Despite the marked difference in scene statistics, we were able to decode scene category from fMRI data for line drawings just as well as from activity for color photographs, in primary visual cortex through PPA and RSC. Even more remarkably, in PPA and RSC, error patterns for decoding from line drawings were very similar to those from color photographs. These data suggest that, in these regions, the information used to distinguish scene category is similar for line drawings and photographs. To determine the relative contributions of local and global structure to the human ability to categorize scenes, we selectively removed long or short contours from the line drawings. In a category-matching task, participants performed significantly worse when long contours were removed than when short contours were removed. We conclude that global scene structure, which is preserved in line drawings, plays an integral part in representing scene categories.

There is evidence that brain cholesterol metabolism modulates the vulnerability for Alzheimer's disease (AD). Previous data showed that brain β-amyloid load in elderly subjects with the CYP46 (cholesterol 24S-hydroxylase) TT-positive genotype was higher than in CYP46 TT-negative elderly subjects. We investigated effects of the CYP46 T/C polymorphism on parahippocampal and hippocampal grey matter (GM) morphology in 81 young subjects using structural magnetic resonance imaging based morphometry. We found that young TT-homozygotes exhibited smallest and CC-homozygotes largest parahippocampal and hippocampal GM volumes with the volumes of the CT-heterozygotes ranging in between. Parahippocampal and hippocampal volumes were positively correlated with delayed memory performance in C-carriers and negatively with immediate memory performance in TT-homozygotes. It has been shown that the brain cholesterol metabolism in general modulates dendrite outgrowth, synaptogenesis, and neuron survival, and it was suggested that CYP46 indirectly influences β-amyloid metabolism. CYP46 C-carriers are privileged both in terms of β-amyloid metabolism and in terms of brain reserve due to their larger parahippocampal and hippocampal structures. The exact cellular mechanisms that translate the CYP46 allelic variation into volumetric brain differences in the parahippocampal gyrus and hippocampus are still unknown and need to be further investigated., (Copyright © 2009 Elsevier Inc. All rights reserved.)

The presubiculum is one of the important regions of the parahippocampal area known to be responsible for processing and integrating spatial representation information. To understand better the functional roles played by the presubiculum, it is essential to elucidate how output signals from the presubiculum distribute to its target regions. In the present study, the axonal branching patterns of single pyramidal neurons in layer V of the rat presubiculum were investigated by using in vivo injection of a viral vector expressing membrane-targeted palmitoylation site-attached green fluorescent protein. We found that individual layer V neurons provide axonal branches to one or two cortical areas with one or more recurrent collaterals to the presubiculum. These neurons were classified into six types, based on their axonal collateralization pattern: neurons with axon branches to 1) both the retrosplenial granular cortex and the parasubiculum, 2) both the retrosplenial granular cortex and the subiculum, and 3) both the medial entorhinal area and the subiculum, and neurons with axonal branches terminating only in 4) the retrosplenial granular cortex, 5) the subiculum, and 6) the presubiculum. Types 1-5 also provide recurrent axons to the presubiculum. Our data demonstrate that layer V of the presubiculum consists of at least six types of cortical projection neurons with various patterns of axonal collateralization. These findings suggest that single presubicular layer V neurons may distribute information to one or two cortical areas participating in the neural circuitry of spatial representation and also send such information back to the presubiculum itself., (Copyright © 2010 Wiley-Liss, Inc.)

The temporal pole (TP) is the rostralmost portion of the human temporal lobe. Characteristically, it is only present in human and nonhuman primates. TP has been implicated in different cognitive functions such as emotion, attention, behavior, and memory, based on functional studies performed in healthy controls and patients with neurodegenerative diseases through its anatomical connections (amygdala, pulvinar, orbitofrontal cortex). TP was originally described as a single uniform area by Brodmann area 38, and von Economo (area TG of von Economo and Koskinas), and little information on its cytoarchitectonics is known in humans. We hypothesize that 1) TP is not a homogenous area and we aim first at fixating the precise extent and limits of temporopolar cortex (TPC) with adjacent fields and 2) its structure can be correlated with structural magnetic resonance images. We describe here the macroscopic characteristics and cytoarchitecture as two subfields, a medial and a lateral area, that constitute TPC also noticeable in 2D and 3D reconstructions. Our findings suggest that the human TP is a heterogeneous region formed exclusively by TPC for about 7 mm of the temporal tip, and that becomes progressively restricted to the medial and ventral sides of the TP. This cortical area presents topographical and structural features in common with nonhuman primates, which suggests an evolutionary development in human species.

Although brain structures involved in central nervous olfactory processing in humans have been well identified with functional neuroimaging, little is known about the temporal sequence of their activation. We recorded olfactory event-related potentials (ERP) to H(2)S stimuli presented to the left and right nostril in 12 healthy subjects. Topographic and source analysis identified four distinct processing steps between 200 and 1000 ms. Activation started ipsilateral to the stimulated nostril in the mesial and lateral temporal cortex (amygdala, parahippocampal gyrus, superior temporal gyrus, insula). Subsequently, the corresponding structures on the contralateral side became involved, followed by frontal structures at the end of the activation period. Thus, based on EEG-related data, current results suggest that olfactory information in humans is processed first ipsilaterally to the stimulated nostril and then activates the major relays in olfactory information processing in both hemispheres. Most importantly, the currently described techniques allow the investigation of the spatial processing of olfactory information at a high temporal resolution., (Copyright 2010 IBRO. All rights reserved.)

Background: The physiopathological mechanism underlying the tinnitus phenomenon is still the subject of an ongoing debate. Since oscillatory EEG activity is increasingly recognized as a fundamental hallmark of cortical integrative functions, this study investigates deviations from the norm of different resting EEG parameters in patients suffering from chronic tinnitus., Results: Spectral parameters of resting EEG of male tinnitus patients (n = 8, mean age 54 years) were compared to those of age-matched healthy males (n = 15, mean age 58.8 years). On average, the patient group exhibited higher spectral power over the frequency range of 2-100 Hz. Using LORETA source analysis, the generators of delta, theta, alpha and beta power increases were localized dominantly to left auditory (Brodmann Areas (BA) 41,42, 22), temporo-parietal, insular posterior, cingulate anterior and parahippocampal cortical areas., Conclusions: Tinnitus patients show a deviation from the norm of different resting EEG parameters, characterized by an overproduction of resting state delta, theta and beta brain activities, providing further support for the microphysiological and magnetoencephalographic evidence pointing to a thalamocortical dysrhythmic process at the source of tinnitus. These results also provide further confirmation that reciprocal involvements of both auditory and associative/paralimbic areas are essential in the generation of tinnitus.

The medial temporal lobe (MTL), a set of heavily interconnected structures including the hippocampus and underlying entorhinal, perirhinal and parahippocampal cortex, is traditionally believed to be part of a unitary system dedicated to declarative memory. Recent studies, however, demonstrated perceptual impairments in amnesic individuals with MTL damage, with hippocampal lesions causing scene discrimination deficits, and perirhinal lesions causing object and face discrimination deficits. The degree of impairment on these tasks was influenced by the need to process complex conjunctions of features: discriminations requiring the integration of multiple visual features caused deficits, whereas discriminations that could be solved on the basis of a single feature did not. Here, we address these issues with functional neuroimaging in healthy participants as they performed a version of the oddity discrimination task used previously in patients. Three different types of stimuli (faces, scenes, novel objects) were presented from either identical or different viewpoints. Consistent with studies in patients, we observed increased perirhinal activity when participants distinguished between faces and objects presented from different, compared to identical, viewpoints. The posterior hippocampus, by contrast, showed an effect of viewpoint for both faces and scenes. These findings provide convergent evidence that the MTL is involved in processes beyond long-term declarative memory and suggest a critical role for these structures in integrating complex features of faces, objects, and scenes into view-invariant, abstract representations.

Neuroimaging experiments in humans suggest that regions in parietal cortex and along the posterior midline are functionally connected to the medial temporal lobe and are active during memory retrieval. It is unknown whether macaques have a similar network. We examined functional connectivity in isoflurane-anesthetized macaques to identify a network associated with posterior parahippocampal cortex (PPHC). Functional connectivity was observed between the PPHC and retrosplenial, posterior cingulate, superior temporal gyrus, and inferior parietal cortex. PPHC correlations were distinct from regions in parietal and temporal cortex activated by an oculomotor task. Comparison of macaque and human PPHC correlations revealed similarities that suggest the temporal-parietal region identified in the macaque may share a common lineage with human Brodmann area 39, a region thought to be involved in recollection. These results suggest that macaques and humans may have homologous PPHC-parietal pathways. By specifying the location of the putative macaque homologue in parietal cortex, we provide a target for future physiological exploration of this area's role in mnemonic or alternative processes.

Zen meditation has been associated with low sensitivity on both the affective and the sensory dimensions of pain. Given reports of gray matter differences in meditators as well as between chronic pain patients and controls, the present study investigated whether differences in brain morphometry are associated with the low pain sensitivity observed in Zen practitioners. Structural MRI scans were performed and the temperature required to produce moderate pain was assessed in 17 meditators and 18 controls. Meditators had significantly lower pain sensitivity than controls. Assessed across all subjects, lower pain sensitivity was associated with thicker cortex in affective, pain-related brain regions including the anterior cingulate cortex, bilateral parahippocampal gyrus and anterior insula. Comparing groups, meditators were found to have thicker cortex in the dorsal anterior cingulate and bilaterally in secondary somatosensory cortex. More years of meditation experience was associated with thicker gray matter in the anterior cingulate, and hours of experience predicted more gray matter bilaterally in the lower leg area of the primary somatosensory cortex as well as the hand area in the right hemisphere. Results generally suggest that pain sensitivity is related to cortical thickness in pain-related brain regions and that the lower sensitivity observed in meditators may be the product of alterations to brain morphometry from long-term practice.

The parahippocampal place area (PPA) is a region of human cortex that responds more strongly to visual scenes (e.g., landscapes or cityscapes) than to other visual stimuli. It has been proposed that the primary function of the PPA is encoding of contextual information about object co-occurrence. Supporting this context hypothesis are reports that the PPA responds more strongly to strong-context than to weak-context objects and more strongly to famous faces (for which contextual associations are available) than to nonfamous faces. We reexamined the reliability of these 2 effects by scanning subjects with functional magnetic resonance imaging while they viewed strong- and weak-context objects, scrambled versions of these objects, and famous and nonfamous faces. "Contextual" effects for objects were observed to be reliable in the PPA at slow presentation rates but not at faster presentation rates intended to discourage scene imagery. We were unable to replicate the earlier finding of preferential PPA response to famous versus nonfamous faces. These results are difficult to reconcile with the hypothesis that the PPA encodes contextual associations but are consistent with a competing hypothesis that the PPA encodes scenic layout.

The essential role of the medial temporal lobe (MTL) in long-term memory for individual events is well established, yet important questions remain regarding the mnemonic functions of the component structures that constitute the region. Within the hippocampus, recent functional neuroimaging findings suggest that formation of new memories depends on the dentate gyrus and the CA(3) field, whereas the contribution of the subiculum may be limited to retrieval. During encoding, it has been further hypothesized that structures within MTL cortex contribute to encoding in a content-sensitive manner, whereas hippocampal structures may contribute to encoding in a more domain-general manner. In the current experiment, high-resolution fMRI techniques were utilized to assess novelty and subsequent memory effects in MTL subregions for two classes of stimuli--faces and scenes. During scanning, participants performed an incidental encoding (target detection) task with novel and repeated faces and scenes. Subsequent recognition memory was indexed for the novel stimuli encountered during scanning. Analyses revealed voxels sensitive to both novel faces and novel scenes in all MTL regions. However, similar percentages of voxels were sensitive to novel faces and scenes in perirhinal cortex, entorhinal cortex, and a combined region comprising the dentate gyrus, CA(2), and CA(3), whereas parahippocampal cortex, CA(1), and subiculum demonstrated greater sensitivity to novel scene stimuli. Paralleling these findings, subsequent memory effects in perirhinal cortex were observed for both faces and scenes, with the magnitude of encoding activation being related to later memory strength, as indexed by a graded response tracking recognition confidence, whereas subsequent memory effects were scene-selective in parahippocampal cortex. Within the hippocampus, encoding activation in the subiculum correlated with subsequent memory for both stimulus classes, with the magnitude of encoding activation varying in a graded manner with later memory strength. Collectively, these findings suggest a gradient of content sensitivity from posterior (parahippocampal) to anterior (perirhinal) MTL cortex, with MTL cortical regions differentially contributing to successful encoding based on event content. In contrast to recent suggestions, the present data further indicate that the subiculum may contribute to successful encoding irrespective of event content.

fMRI studies of recognition memory have often been interpreted to mean that the hippocampus selectively subserves recollection and that adjacent regions selectively subserve familiarity. Yet, many of these studies have confounded recollection and familiarity with strong and weak memories. In a source memory experiment, we compared correct source judgments (which reflect recollection) and incorrect source judgments (often thought to reflect familiarity) while equating for old-new memory strength by including only high-confidence hits in the analysis. Hippocampal activity associated with both correct source judgments and incorrect source judgments exceeded the activity associated with forgotten items and did so to a similar extent. Further, hippocampal activity was greater for high-confidence old decisions relative to forgotten items even when source decisions were at chance. These results identify a recollection signal in the hippocampus and may identify a familiarity signal as well. Similar results were obtained in the parahippocampal gyrus. Unlike in the medial temporal lobe, activation in prefrontal cortex increased differentially in association with source recollection.

We investigated the cortical efferents of the parahippocampal region by placing injections of the anterograde tracers, Phaseolus vulgaris-leuccoagglutinin, and biotinylated dextran amine, throughout the perirhinal (PER), postrhinal (POR), and entorhinal cortices of the rat brain. The resulting density of labeled fibers was evaluated in 25 subregions of the piriform, frontal, insular, temporal, cingulate, parietal, and occipital areas. The locations of labeled terminal fibers differed substantially depending on whether the location of the injection site was in PER area 35, PER area 36, POR, or the lateral or the medial entorhinal (LEA and MEA). The differences were greater for sensory regions. For example, the POR efferents preferentially target visual and spatial regions, whereas the PER efferents target all sensory modalities. The cortical efferents of each region largely reciprocate the cortical afferents, though the degree of reciprocity varied across originating and target regions. The laminar pattern of terminal fibers was consistent with the notion that the efferents are feedback projections. The density and amount of labeled fibers also differed substantially depending on the regional location of injection sites. PER area 36 and POR give rise to a greater number of heavy projections, followed by PER area 35. LEA also gives rise to widespread cortical efferents, arising mainly from a narrow band of cortex adjacent to the PER. In contrast, the remainder of the LEA and the MEA provides only weak efferents to cortical regions. Prior work has shown that nonspatial and spatial information is transmitted to the hippocampus via the PER-LEA and POR-MEA pathways, respectively. Our findings suggest that the return projections follow the same pathways, though perhaps with less segregration.

Background: Access to lesions located in the atrium of the lateral ventricle without causing neurologic deficit can be challenging. Here, we demonstrate the supracerebellar transtentorial transcollateral sulcus (STTS) approach as an alternative route to the atrium of the lateral ventricle using anatomical dissections in cadavers., Methods: Suboccipital craniotomy with extension above the transverse sinus was performed in 5 arterial and venous latex-injected cadaveric heads (10 hemispheres). After the dural opening, arachnoidal dissection of the supracerebellar space was performed, and the tentorium cerebelli was cut from lateral to medial. This revealed the parahippocampal and fusiform gyri and collateral sulcus (CS). The distance from the CS to the atrium was measured., Results: The atrium of the lateral ventricle was entered through the CS in each specimen. The cerebral hemispheres were removed from each cadaveric specimen, and dissections were performed. The distance from the CS to the atrium was 1.30 cm on the right side and 1.31 cm on the left. The CS was bifurcated in 62% of the hemispheres, whereas it was single in 38%. Through this approach, only the "u" fibers of the CS were damaged, and the fibers of the optic radiation in the inferolateral wall of the atrium were preserved., Conclusion: The STTS approach may be an effective alternative approach to lesions located in the medioposterior aspect of the atrium of the lateral ventricle in selected cases. Further clinical studies to evaluate the safety and efficacy of this approach are needed.

Purpose: Exposure of the cavernous sinus or anterior parahippocampus often involves a wide exposure of the temporal lobe and mobilization of the temporalis muscle associated with temporal lobe retraction. The authors present a cadaveric study to illustrate the feasibility, advantages and landmarks necessary to perform a trans-zygomatic middle fossa approach to lesions around the cavernous sinus and anterior parahippocampus., Methods: The authors performed bilateral trans-zygomatic middle fossae exposures to reach the cavernous sinus and parahippocampus in five cadavers (10 sides). We assessed the morbidity associated with this procedure and compared the indications, advantages, and disadvantages of this method versus more extensive skull base approaches. A vertical linear incision along the middle portion of the zygomatic arch was extended one finger breadth inferior to the inferior edge of the zygomatic arch. Careful dissection inferior to the arch allowed preservation of facial nerve branches. A zygomatic osteotomy was followed via a linear incision through the temporalis muscle and exposure of the middle cranial fossa floor., Results: A craniotomy along the inferolateral temporal bone and middle fossa floor allowed extradural dissection along the middle fossa floor and exposure of the cavernous sinus including all three divisions of the trigeminal nerve. Intradural inspection demonstrated adequate exposure of the parahippocampus. Exposure of the latter required minimal or no retraction of the temporal lobe., Conclusions: The trans-zygomatic middle fossa approach is a simplified skull base exposure using a linear incision, which may avoid the invasivity of more extensive skull base approaches while providing an adequate corridor for resection of cavernous sinus and parahippocampus lesions. The advantages of this approach include its efficiency, ease, minimalism, preservation of the temporalis muscle, and minimal retraction of the temporal lobe.

Content and function words have different roles in language and differ greatly in their semantic content. Although previous research has suggested that these different roles may be mediated by different neural substrates, the neuroimaging literature on this topic is particularly scant. Moreover, fMRI studies that have investigated differences between content and function words have utilized tasks that focus the subjects' attention on the differences between these word types. It is possible, then, that task-related differences in attention, working memory, and decision-making contribute to the differential patterns of activation observed. Here, subjects were engaged in a continuous working memory cover task while single, task-irrelevant content and function words were infrequently and irregularly presented. Nonword letter strings were displayed in black font at a fast rate (2/s). Subjects were required to either remember or retrieve occasional nonwords that were presented in colored fonts. Incidental and irrelevant to the memory task, content and function words were interspersed among nonwords at intervals of 12 to 15 s. Both word types strongly activated temporal-parietal cortex, middle and anterior temporal cortex, inferior frontal gyrus, parahippocampal gyrus, and orbital frontal cortex. Activations were more extensive in the left hemisphere. Content words elicited greater activation than function words in middle and anterior temporal cortex, a sub-region of orbital frontal cortex, and the parahippocampal region. Words also evoked extensive deactivation, most notably in brain regions previously associated with working memory and attention.

Several quantitative MRI-based protocols have been developed for measuring the volume of entorhinal (ERC), perirhinal (PRC), and posterior parahippocampal (PPHC) cortex. However, since the volume of a cortical region is a composite measure, relating directly to both thickness and surface area, it would be ideal to be able to quantify all of these morphometric measures, particularly since disease-related processes, such as Alzheimer's disease (AD), may preferentially affect thickness. This study describes a novel protocol for measuring the thickness, surface area, and volume of these three medial temporal lobe (MTL) subregions. Participants included 29 younger normal subjects (ages 18-30), 47 older normal subjects (ages 66-90), and 29 patients with mild AD (ages 56-90). Cortical surface models were reconstructed from the gray/white and gray/cerebrospinal fluid boundaries, and a hybrid visualization approach was implemented to trace the ERC, PRC, and PPHC using both orthogonal MRI slice- and cortical surface-based visualization of landmarks. Anatomic variants of the collateral sulcus (CS) were classified in all 105 participants, and the relationship between CS variants and corresponding morphometric measures was examined. One CS variant - deep, uninterrupted CS not connected with nearby sulci - was the most common configuration and was associated with thinner cortex within the ERC and PRC regions. This novel protocol enables the reliable measurement of both the thickness and surface area of ERC, PRC, and PPHC.