Transient global amnesia: 7 Tesla MRI reveals more hippocampal lesions with diffusion restriction compared to 1.5 and 3 Tesla MRI.

PURPOSE: To assess the ability of 7 T MRI to detect hippocampal DWI lesions in the acute phase of TGA compared to 1.5 T/3 T MRI. METHODS: Patients with a clinical diagnosis consistent with TGA and a 1.5/3 T MRI underwent an additional 7 T MRI when the 7 T system was available for clinical use, thus serving as their own controls. RESULTS: Thirteen TGA patients with a median age of 68.5 years (range 46-77 years) were included and imaged at 1.5/3 T (median 17 h after onset of symptoms, range 3-23 h) and 7 T (median 23 h after onset, range 15-46 h). The 7 T MRIs were performed a median of 15 h after the 1.5/3 T MRIs (range 1-28 h). At 1.5/3 T, six patients (46%) were found to have at least one hippocampal DWI-lesions supporting the TGA diagnosis, which increased to 11 patients (85%) when examined at 7 T (p = 0.03). At 1.5/3 T, nine hippocampal DWI lesions were detected, which increased to 19 at 7 T, giving an increased detection rate of 111% (p = 0.002). Both neuroradiologists found the hippocampal DWI lesions at 7 T to have higher conspicuity and be easier to categorize as true findings compared to 1.5/3 T. CONCLUSION: Seven-Tesla MRI showed both a statistically significant increase in the total number of detected hippocampal DWI lesions and the proportion of patients with at least one hippocampal DWI lesion supporting the TGA diagnosis compared to 1.5/3 T. Clinical use of 7 T will increase the number of patients having their TGA diagnosis supported by MRI, which can be especially useful in patients with negative 1.5/3 T MRI and low clinical certainty.

Entorhinal Layer II Calbindin-Expressing Neurons Originate Widespread Telencephalic and Intrinsic Projections.

In the present study we provide the first systematic and quantitative hodological study of the calbindin-expressing (CB+) principal neurons in layer II of the entorhinal cortex and compared the respective projections of the lateral and medial subdivisions of the entorhinal cortex. Using elaborate quantitative retrograde tracing, complemented by anterograde tracing, we report that the layer II CB+ population comprises neurons with diverse, mainly excitatory projections. At least half of them originate local intrinsic and commissural projections which distribute mainly to layer I and II. We further show that long-range CB+ projections from the two entorhinal subdivisions differ substantially in that MEC projections mainly target field CA1 of the hippocampus, whereas LEC CB+ projections distribute much more widely to a substantial number of known forebrain targets. This connectional difference between the CB+ populations in LEC and MEC is reminiscent of the overall projection pattern of the two entorhinal subdivisions.

Convergent Projections from Perirhinal and Postrhinal Cortices Suggest a Multisensory Nature of Lateral, but Not Medial, Entorhinal Cortex.

The current model of the organization of the medial temporal lobe (MTL) episodic memory system assumes that two functionally different "where" and "what" pathways enter MTL as parallel parahippocampal cortex (PHC)-medial entorhinal cortex (MEC) and perirhinal cortex (PER)-lateral entorhinal cortex (LEC) streams, respectively. With the use of tract tracing and in vitro electrophysiological recordings, we show that, in the rat LEC, all main principal neuron types in layer II receive convergent inputs from PER and postrhinal cortex (POR), homologous to PHC in primates. Projections to MEC from POR are much less prominent than previously assumed. These findings thus challenge the prevailing concept that LEC and MEC are defined by different inputs from the PER and PHC/POR, respectively. Our findings point to LEC as the main parahippocampal multimodal integrative structure whose unique set of external sensory-derived inputs allows its network to represent a continuously fluctuating extrinsic environment.

Neurons and networks in the entorhinal cortex: A reappraisal of the lateral and medial entorhinal subdivisions mediating parallel cortical pathways.

In this review, we aim to reappraise the organization of intrinsic and extrinsic networks of the entorhinal cortex with a focus on the concept of parallel cortical connectivity streams. The concept of two entorhinal areas, the lateral and medial entorhinal cortex, belonging to two parallel input-output streams mediating the encoding and storage of respectively what and where information hinges on the claim that a major component of their cortical connections is with the perirhinal cortex and postrhinal or parahippocampal cortex in, respectively, rodents or primates. In this scenario, the lateral entorhinal cortex and the perirhinal cortex are connectionally associated and likewise the postrhinal/parahippocampal cortex and the medial entorhinal cortex are partners. In contrast, here we argue that the connectivity matrix emphasizes the potential of substantial integration of cortical information through interactions between the two entorhinal subdivisions and between the perirhinal and postrhinal/parahippocampal cortices, but most importantly through a new observation that the postrhinal/parahippocampal cortex projects to both lateral and medial entorhinal cortex. We suggest that entorhinal inputs provide the hippocampus with high-order complex representations of the external environment, its stability, as well as apparent changes either as an inherent feature of a biological environment or as the result of navigating the environment. This thus indicates that the current connectional model of the parahippocampal region as part of the medial temporal lobe memory system needs to be revised.

Architecture of the Entorhinal Cortex A Review of Entorhinal Anatomy in Rodents with Some Comparative Notes.

The entorhinal cortex (EC) is the major input and output structure of the hippocampal formation, forming the nodal point in cortico-hippocampal circuits. Different division schemes including two or many more subdivisions have been proposed, but here we will argue that subdividing EC into two components, the lateral EC (LEC) and medial EC (MEC) might suffice to describe the functional architecture of EC. This subdivision then leads to an anatomical interpretation of the different phenotypes of LEC and MEC. First, we will briefly summarize the cytoarchitectonic differences and differences in hippocampal projection patterns on which the subdivision between LEC and MEC traditionally is based and provide a short comparative perspective. Second, we focus on main differences in cortical connectivity, leading to the conclusion that the apparent differences may well correlate with the functional differences. Cortical connectivity of MEC is features interactions with areas such as the presubiculum, parasubiculum, retrosplenial cortex (RSC) and postrhinal cortex, all areas that are considered to belong to the "spatial processing domain" of the cortex. In contrast, LEC is strongly connected with olfactory areas, insular, medial- and orbitofrontal areas and perirhinal cortex. These areas are likely more involved in processing of object information, attention and motivation. Third, we will compare the intrinsic networks involving principal- and inter-neurons in LEC and MEC. Together, these observations suggest that the different phenotypes of both EC subdivisions likely depend on the combination of intrinsic organization and specific sets of inputs. We further suggest a reappraisal of the notion of EC as a layered input-output structure for the hippocampal formation.

Excitatory Postrhinal Projections to Principal Cells in the Medial Entorhinal Cortex.

The postrhinal cortex (POR) provides substantial input to the entorhinal cortex, mainly targeting superficial layers of the medial entorhinal cortex (MEC). Major inputs to POR originate in the visual and parietal cortex, thus providing neurons in MEC with a subset of cortical information relevant to their spatial firing properties. The POR takes a position that is comparable with that of the perirhinal cortex (PER) with regard to the lateral entorhinal cortex (LEC). Neurons in LEC and MEC show different functional properties likely reflecting differences in their respective inputs. Projections from PER to LEC exert a main inhibitory influence, which may relate to the sparse object-selective firing in LEC. In view of the continuous, spatially modulated firing properties of principal neurons in MEC, we tested in rats the hypothesis that projections from POR to MEC are functionally different from the PER-to-LEC counterpart in providing an excitatory drive to MEC. Our combined confocal and quantitative electron-microscopic observations indicated that POR projections target mainly principal cells in MEC, including neurons that project to the hippocampus. The ultrastructure of the majority of the synapses indicated that they are excitatory. Voltage-sensitive dye imaging in sagittal slices confirmed this morphologically derived conclusion, showing that the MEC network always responded with an overall depolarization, indicative for net excitatory transmission. In vitro single-cell recordings from principal cells showed only excitatory responses upon POR stimulation. These results show that POR provides an excitatory projection to MEC, differing fundamentally from the inhibitory projection of PER to LEC.