The Parahippocampal-Hippocampal Region: Differentation in Structure and Function

Witter, M.P. [Promotor

A Specific Role of the Human Hippocampus in Recall of Temporal Sequences

There is a growing interest in how temporal order of episodic memories is represented within the medial temporal lobe (MTL). Animal studies suggest that the hippocampal formation (HF) is critical for retrieving the temporal order of past experiences. However, human imaging studies that have tested recency discrimination between pairs of previously encoded items have generally failed to report HF activation. We hypothesized that recalling a naturalistic sequence of past events would be particularly sensitive to HF function, attributable to greater involvement of associative processes. To test this prediction, we let subjects watch a novel movie and later, during functional magnetic resonance imaging, asked them to rearrange and "replay" scenes from the movie in correct order. To identify areas specifically involved in retrieval of temporal order, we used a control condition where subjects logically inferred the order of scenes from the same movie. Extensive MTL activation was observed during sequence recall. Activation within the right HF was specifically related to retrieval of temporal order and correlated positively with accuracy of sequence recall. Also, the bilateral parahippocampal cortex responded to retrieval of temporal order, but the activation here was not related to performance. Our study is the first to unequivocally demonstrate that correct sequence recall depends on H

A structural MRI study in monozygotic twins concordant or discordant for attention/hyperactivity problems: Evidence for genetic and environmental heterogeneity in the developing brain.

Several structural brain abnormalities have been reported in patients with Attention Deficit Hyperactivity Disorder (ADHD). However, the etiology of these brain changes is still unclear. To investigate genetic and environmental influences on ADHD related neurobiological changes, we performed Voxel-Based Morphometry on MRI scans from monozygotic (MZ) twins selected from a large longitudinal population database to be highly concordant or highly discordant for ratings on the Child Behavior Checklist Attention Problem scale (CBCL-AP). Children scoring low on the CBCL-AP are at low risk for ADHD, whereas children scoring high on this scale are at high-risk for ADHD. Brain differences between concordant high-risk twin pairs and concordant low-risk twin pairs likely reflect the genetic risk for ADHD; brain differences between the low-risk and high-risk twins from discordant MZ twin pairs reflect the environmental risk for ADHD. A major difference between comparisons of high and low-risk twins from concordant pairs and high/low twins from discordant pairs was found for the prefrontal lobes. The concordant high-risk pairs showed volume loss in orbitofrontal subdivisions. High-risk members from the discordant twin pairs exhibited volume reduction in the right inferior dorsolateral prefontal cortex. In addition, the posterior corpus callosum was compromised in concordant high-risk pairs, only. Our findings indicate that inattention and hyperactivity symptoms are associated with anatomical abnormalities of a distributed action-attentional network. Different brain areas of this network appear to be affected in inattention/hyperactivity caused by genetic (i.e., high concordant MZ pairs) vs. environmental (i.e., high-low discordant MZ pairs) risk factors. These results provide clues that further our understanding of brain alterations in ADHD. © 2007 Elsevier Inc. All rights reserved

Activation of the human medial temporal lobes by stereoscopic depth cues

The perirhinal cortex (PER) is part of both the medial temporal lobe memory system (MTL) and the ventral visual stream (VVS). In the MTL, PER provides input to the hippocampal formation directly and via the entorhinal cortex (EC), whereas in the VVS, PER is considered to be at the top of the visual processing hierarchy of object information. Because of its position in both networks, PER presumably serves a role in memory and visual perception. PER's perceptual role is thought to be contingent upon the complexity of visual information, i.e., PER only becomes active in visual perception when many higher order visual cues are combined. Using high-resolution functional MRI (fMRI), we investigated the effect of varying the presence of binocular disparity, in complex visual object stimuli. Nineteen subjects were presented with movies of complex objects and a fixation cross, either with or without binocular disparity (referred to as stereo and mono condition respectively). Subjects were instructed to attentively watch the objects, but no instructions were given to memorize them. Group results showed increased activity in the MTL, among which is PER, when comparing the stereo over the mono condition (stereo > mono). Individual analysis showed dominant activation in the stereo > mono contrast in eleven out of nineteen subjects, whereas only three subjects showed dominance in the opposite contrast.We conclude that the MTL is differentially activated by the stereo and mono condition, such that activation is stronger when a complex visual object stimulus with disparity is presented

The anatomy of memory: an interactive overview of the parahippocampal-hippocampal network

Converging evidence suggests that each parahippocampal and hippocampal subregion contributes uniquely to the encoding, consolidation and retrieval of declarative memories, but their precise roles remain elusive. Current functional thinking does not fully incorporate the intricately connected networks that link these subregions, owing to their organizational complexity; however, such detailed anatomical knowledge is of pivotal importance for comprehending the unique functional contribution of each subregion. We have therefore developed an interactive diagram with the aim to display all of the currently known anatomical connections of the rat parahippocampal-hippocampal network. In this Review, we integrate the existing anatomical knowledge into a concise description of this network and discuss the functional implications of some relatively underexposed connections

Hippocampal formation

The hippocampal formation and parahippocampal region are prominent components of the rat nervous system and play a crucial role in learning, memory, and spatial navigation. Many new details regarding the entorhinal cortex have been discovered since the previous edition, and the growing interest in the area of CA2 has been covered in this chapter. Emphasis is on a conceptual change: instead of perceiving the hippocampal circuit as the standard sequential processing network, current insights favor the concept that multiple parallel networks are present. Many new facts, combined with a thorough restructuring of information and inclusion of pointers to relevant (online) resources, make this chapter relevant to both the novice and senior readership

Graph analysis of the anatomical network organization of the hippocampal formation and parahippocampal region in the rat

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