Unfolding the cognitive map: The role of hippocampal and extra-hippocampal substrates based on a systems analysis of spatial processing.

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.

Concomitant occurrence of FXTAS and clinically defined sporadic inclusion body myositis: report of two cases.

This report describes unique presentations of inclusion body myositis (IBM) in two unrelated patients, one male and one female, with genetically and histologically confirmed fragile X-associated tremor/ataxia syndrome (FXTAS). We summarize overlapping symptoms between two disorders, clinical course, and histopathological analyses of the two patients with FXTAS and sporadic IBM, clinically defined per diagnostic criteria of the European Neuromuscular Centre. In case 1, a post-mortem analysis of available brain and muscle tissues is also described. Histopathological features (rimmed vacuoles) consistent with clinically defined IBM were detected in both presented cases. Postmortem testing in case 1 revealed the presence of an FMR1 premutation allele of 60 CGG repeats in both brain and skeletal muscle samples. Case 2 was a premutation carrier with 71 CGG repeats who had a son with FXS. Given that FXTAS is associated with immune-mediated disorders among premutation carriers, it is likely that the pathogeneses of IBM and FXTAS are linked. This is, to our knowledge, the first report of these two conditions presenting together, which expands our understanding of clinical symptoms and unusual presentations in patients with FXTAS. Following detection of a premutation allele of the FMR1 gene, FXTAS patients with severe muscle pain should be assessed for IBM.