Laminar Specificity of Intrinsic Connections in Broca's Area

Broca's area and its right hemisphere homologue comprise 2 cytoarchitectonic subdivisions, FDΓ and FCBm of von Economo C and Koskinas GN (1925, Die Cytoarchitektonik der Hirnrinde des erwachsenen Menschen. Vienna/Berlin [Germany]: Springer). We report here on intrinsic connections within these areas, as revealed with biotinylated dextran amine and 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate tracing in postmortem human brains. Injections limited to supragranular layers revealed a complex intrinsic network of horizontal connections within layers II and III spreading over several millimeters and to a lesser extent within layers IV, V, and VI. Ninety percent of the retrogradely labeled neurons (n = 734) were in supragranular layers, 4% in layer IV, and 6% in infragranular layers; most were pyramids and tended to be grouped into clusters of approximately 500 μm in diameter. Injections involving layer IV revealed extended horizontal connections within layers I-IV (up to 3.7 mm) and to a lesser extent in layers V and VI. Injections limited to the infragranular layers revealed horizontal connections mainly limited to these layers. Thus, intrinsic connections within Broca's area display a strong laminar specificity. This pattern is very similar in areas FDΓ and FCBm and in the 2 hemisphere

Hippocampal sclerosis dementia: a reappraisal

Hippocampal sclerosis (HpScl) is characterized by neuronal loss and gliosis in CA1 and subiculum of the hippocampus, and may be one contributing factor to dementia in old age. The term hippocampal sclerosis dementia (HpSclD) designates the presence of both hippocampal sclerotic lesions and a dementia syndrome. In the present review, we outline the pathological heterogeneity underlying HpSclD and discuss related disorders due to tau protein pathology and frontotemporal dementia with ubiquitin positive inclusions (FTLD-U). We also provide a detailed morphological description of ten of our own autopsied HpSclD cases, and compare these pathological findings with those reported in the literature. The lateralization of HpScl and the atrophy of the mammillary bodies were striking features in most of our cases. The main pathology consisted of tau positive lesions with a predominance of neuronal and glial pretangles in Ammon's horn and the dentate gyrus. Neurofibrillary and ghost tangles in CA1 and the subiculum were scarce and thus insufficient to explain the hippocampal pyramidal cell loss. In some cases, tau pathology in the hippocampal formation coexisted with glial tau pathology in the frontal cortex. The most striking finding besides the tau pathology was the presence of concomitant neuronal cytoplasmic inclusions and neurites immunoreactive for the transactive response DNA-binding protein-43 (TDP-43) in the dentate gyrus and temporal neocortex, similar to those found in FTLD-U. Taken together, the pathology of HpSclD is indicative of a degenerative rather than a hypoxic/ischemic etiology of HpSclD. Presently, HpSclD may best be deemed a disorder with various neurodegenerative etiologies, most notably tauopathy and TDP-43 proteinopathy (i.e. FTLD-U). Each of these disease processes could either independently or concertedly account for the dementia syndrome in HpScl

Intrinsic connectivity of human superior colliculus

The superior colliculus (SC) is believed to play an important role in sensorimotor integration and orienting behavior. It is classically divided into superficial layers predominantly containing visual neurons and deep layers containing multisensory and premotor neurons. Investigations of intrinsic connectivity within the SC in non-human species initially led to controversy regarding the existence of interlaminar connections between superficial and deep layers. It now seems more likely that such connections exist in a number of species, including non-human primates. In the latter, anatomical data concerning intrinsic SC connectivity are restricted to a limited number of intracellularly labeled neurons. No studies have been conducted to investigate the existence of intrinsic connections of human SC. In the present study, DiI (1,1′-dioctadecyl-3,3,3′,3′- tetramethylindocarbocyanine perchlorate) and BDA (biotinylated dextran amine) were two tracers used in post-mortem human brains to examine intrinsic SC connections. Injections into the superficial layers revealed tangential connections within superficial layers and radial superficial-layer to deep-layer connections. Within superficial layers, horizontal connections were found over the entire rostro-caudal axis and were mostly directed laterally, i.e. toward the brachium of the inferior colliculus. Superficial-layer to deep-layer connections were more prominent in sections containing the injection site or located close to it. In these sections, an axon bundle having roughly the same diameter as the injection site crossed all deep layers, and individual axons displayed en passant or terminal boutons. The present results suggest that intrinsic connections within superficial layers and radial superficial-layers to deep-layers exist in human SC. The putative roles of these connections are discussed with regard to visual receptive field organization, as well as visuomotor and multisensory integratio

Argyrophilic grain disease: molecular genetic difference to other four-repeat tauopathies

Argyrophilic grain disease (AgD) is a four-repeat tauopathy that is almost exclusively restricted to allocortical areas. Progressive supranuclear palsy and corticobasal degeneration also show predominant deposition of four-repeat tau filaments, and are associated with the tau H1 haplotype. We investigated a possible association between AgD and the tau H1 haplotype. In AgD, no difference between the prevalence of the tau H1 haplotype or H1/H1 genotype was observed when compared to non-demented control cases. These data suggest that a dysfunction of the tau protein in AgD—in contrast to other four-repeat tauopathies—may arise irrespective of the genetic background regarding the tau H1 or H2 haplotype

Histological markers in nasal mucosa of patients with Alzheimer's disease

Neuropathological changes such as dystrophic neurites and the presence of abnormal tau protein in the olfactory system, including primary sensory cells and nerve fibres have previously been demonstrated in nasal mucosa tissue of patients with Alzheimer's disease (AD). These changes were detected in autopsy-derived material from histopathologically confirmed AD cases as well as in biopsy tissue from clinical severely ill AD patients. To investigate the potential usefulness for the early diagnosis of AD, we obtained biopsy tissue from olfactory mucosa from 5 clinically mild to moderate AD patients and stained for the presence of tau or beta-amyloid by immunocytochemistry using a panel of specific antibodies. No positive staining was found in any of the cases. For comparison, post-mortem olfactory tissue from AD patients with severe neuropathological changes (widespread neurofibrillary tangles and amyloid in the brain) was investigated, in these severe cases, tau immunoreactivity was found in fine nerve fibres in the lamina propria and in a few olfactory epithelial cells. These results are consistent with other reports showing that cytoskeletal changes and tau pathology in the olfactory epithelium are not primary (or specific) features of AD and may occur predominantly in late stages of the disease

Lobar Dementia due to Extreme Widening of Virchow-Robin Spaces in One Hemisphere

Widened perivascular spaces known as Virchow-Robin spaces (VRS) are often seen on MRI and are usually incidental findings. It is unclear if enlarged VRS can be associated with neurological deficits. In this report, we describe a case of lobar dementia associated with unusual VRS widening in one cerebral hemisphere. A 77-year-old woman, seen at a memory clinic, presented with progressive cognitive decline, left hemianopsia, and mild pyramidal signs on the left side. On MRI, unusually wide VRS were visible, predominantly in the right centrum semiovale and the right temporo-occipital white matter. The clinical syndrome was consistent with the extent and location of the abnormally dilated VRS. The high MR signal in white matter bridges between the VRS suggested parenchymal damage, possibly representing gliotic white matter. No evidence for another etiology was found on cerebral MRI and rCBF SPECT. As a conclusion, enlarged VRS in one cerebral hemisphere may be associated with cognitive change and neurological deficits

Receptor localization in the human hypothalamus

In summary, we have illustrated and discussed the applicability of different techniques to the study of neurotransmitter receptors in the human brain. Because of the availability of these techniques it is possible today to examine in detail the alterations in density produced by different physiological or pathological conditions. The use of these techniques will in the future, without any doubt, be of help in understanding the chemical neuroanatomy of the human hypothalamus.Peer Reviewe