Organization and Detailed Parcellation of Human Hippocampal Head and Body Regions Based on a Combined Analysis of Cyto- and Chemoarchitecture.

The hippocampal formation (HF) is one of the hottest regions in neuroscience because it is critical to learning, memory, and cognition, while being vulnerable to many neurological and mental disorders. With increasing high-resolution imaging techniques, many scientists have started to use distinct landmarks along the anterior-posterior axis of HF to allow segmentation into individual subfields in order to identify specific functions in both normal and diseased conditions. These studies urgently call for more reliable and accurate segmentation of the HF subfields DG, CA3, CA2, CA1, prosubiculum, subiculum, presubiculum, and parasubiculum.

In vivo parahippocampal white matter pathology as a biomarker of disease progression to Alzheimer's disease.

Noninvasive diagnostic tests for Alzheimer's disease (AD) are limited. Postmortem diagnosis is based on density and distribution of neurofibrillary tangles (NFTs) and amyloid-rich neuritic plaques. In preclinical stages of AD, the cells of origin for the perforant pathway within the entorhinal cortex are among the first to display NFTs, indicating its compromise in early stages of AD.

Stratum radiatum of CA2 is an additional target of the perforant path in humans and monkeys.

The perforant path (PP) connects two key components of the medial temporal memory system, the entorhinal cortex and hippocampus. Entorhinal layer II projects densely to the outer portion of the molecular layer of the dentate gyrus and the stratum lacunosum-moleculare of CA2 and CA3 of the hippocampus. This study for the first time reports that the PP terminal zone originated from entorhinal layer II extends from the stratum lacunosum-moleculare into the stratum radiatum in CA2 but not in CA3 in both human and nonhuman primates.

Borders, extent, and topography of human perirhinal cortex as revealed using multiple modern neuroanatomical and pathological markers.

Despite rapidly increasing interests in specific contributions of different components of human medial temporal lobe (MTL) to memory and memory impairments in normal aging and in many abnormal conditions such as Alzheimer's disease and Pick's disease, few modern neuroanatomical studies are available about the borders, extent, and topography of human perirhinal areas 35 and 36, which are important components of the MTL memory system. By a combined use of several cellular, neurochemical, and pathological markers, which mainly include neuronal nuclear antigen, calcium-binding proteins (parvalbumin and calbindin-D28k), nonphosphorylated neurofilament protein (SMI-32), Wisteria floribunda agglutinin, and abnormally phosphorylated tau (AT8), this study has revealed that the borders of human perirhinal areas 35 and 36 are significantly different from those defined with conventional Nissl staining. In general, areas 35 and 36 occupy the ventromedial temporopolar and rhinal sulcal regions, the collateral sulcal region, and the anterior two-thirds of fusiform gyrus or occipitotemporal gyrus.

Parcellation of human temporal polar cortex: a combined analysis of multiple cytoarchitectonic, chemoarchitectonic, and pathological markers.

Although the human temporal polar cortex (TPC), anterior to the limen insulae, is heavily involved in high-order brain functions and many neurological diseases, few studies on the parcellation and extent of the human TPC are available that have used modern neuroanatomical techniques. The present study investigated the TPC with combined analysis of several different cellular, neurochemical, and pathological markers and found that this area is not homogenous, as at least six different areas extend into the TPC, with another area being unique to the polar region. Specifically, perirhinal area 35 extends into the posterior TPC, whereas areas 36 and TE extend more anteriorly.

Loss of nonphosphorylated neurofilament immunoreactivity in temporal cortical areas in Alzheimer's disease.

The distribution of immunoreactive neurons with nonphosphorylated neurofilament protein (SMI32) was studied in temporal cortical areas in normal subjects and in patients with Alzheimer's disease (AD). SMI32 immunopositive neurons were localized mainly in cortical layers II, III, V and VI, and were medium to large-sized pyramidal neurons. Patients with AD had prominent degeneration of SMI32 positive neurons in layers III and V of Brodmann areas 38, 36, 35 and 20; in layers II and IV of the entorhinal cortex (Brodmann area 28); and hippocampal neurons.

Posterior parahippocampal gyrus pathology in Alzheimer's disease.

The posterior parahippocampal gyrus (PPHG) of the non-human primate brain has a distinct dual role in cortical neural systems. On the one hand, it is a critical link in providing the entorhinal cortex and hippocampal formation with cortical input, while on the other hand it receives output from these structures and projects widely by disseminating the medial temporal lobe output to the cortex. Layer III of TF and TH areas largely mediate the former (input) while layer V mediates the latter (output).

The abnormally phosphorylated tau lesion of early Alzheimer's disease.

The perirhinal cortex (area 35) is well-known locus for neurofibrillary tangles (NFT) in initial Alzheimer's disease (AD) and fully developed AD and may contain tau alterations in non-demented elderly. The topography and location of this vulnerable cortex, however, is difficult to appreciate because of its variable architecture and to deviations imposed by temporal sulcal patterns. We have immunostained human brains with a short duration of dementia using antibody AT8, which recognize abnormally hyperphosphorylated tau, calcium binding protein-parvalbumin and other phenotype markers to more fully appreciate the extent of area 35 before it is obscured by pathology.

Thalamic projections to the posteromedial cortex in the macaque.

The medial parietal, posterior cingulate, and retrosplenial cortices collectively constitute a region of cortex referred to as the posteromedial cortices (PMC). In an effort to shed light on the neuroanatomical organization of the PMC, we undertook a study to identify and analyze the thalamocortical connections of these cortices. Retrograde tracer injections were placed in the posterior cingulate (PCC), retrosplenial (RSC), medial parietal cortices (MPC), and posterior cingulate sulcus (PCS), and the labeling patterns within the thalamus were analyzed.

Modular and laminar pathology of Brodmann's area 37 in Alzheimer's disease.

Previous studies suggested a relationship between severity of symptoms and the degree of neurofibrillary tangles (NFTs) clustering in different areas of the cortex in Alzheimer's disease (AD). The posterior inferior temporal cortex or Brodmann's area (BA 37) is involved in object naming and recognition memory. But the cellular architecture and connectivity and the NFT pathology of this cortex in AD received inadequate attention.

Evidence for direct projections from the basal nucleus of the amygdala to retrosplenial cortex in the Macaque monkey.

The role of the primate retrosplenial cortex (RSC) in memory processing and spatial navigation has been well established. Recently, processing emotionally salient information has been attributed to the RSC as well. Little anatomical data, however, exist linking the RSC with known emotional processing centers within the brain.

Amygdala interconnections with the cingulate motor cortex in the rhesus monkey.

Amygdala interconnections with the cingulate motor cortices were investigated in the rhesus monkey. Using multiple tracing approaches, we found a robust projection from the lateral basal nucleus of the amygdala to Layers II, IIIa, and V of the rostral cingulate motor cortex (M3). A smaller source of amygdala input arose from the accessory basal, cortical, and lateral nuclei, which targeted only the rostral region of M3.

Hughlings Jackson and the role of the entorhinal cortex in temporal lobe epilepsy: from patient A to Doctor Z.

Hughlings Jackson's insightful bedside observations of patients with epilepsy paved the way for the first effective surgical epilepsy treatments. Jackson's most famous case, that of Doctor Z, concerned a medical doctor with partial complex seizures who was reported to have a discrete and circumscribed medial temporal lobe (mTL) lesion on autopsy. Although integral to Jackson's argument for mTL resection, the case remains controversial due to inadequate pathological descriptions of Doctor Z's lesion.

Neural connections of the posteromedial cortex in the macaque.

The posterior cingulate and the medial parietal cortices constitute an ensemble known as the posteromedial cortex (PMC), which consists of Brodmann areas 23, 29, 30, 31, and 7m. To understand the neural relationship of the PMC with the rest of the brain, we injected its component areas with four different anterograde and retrograde tracers in the cynomolgus monkey and found that all PMC areas are interconnected with each other and with the anterior cingulate, the mid-dorsolateral prefrontal, the lateral parietal cortices, and area TPO, as well as the thalamus, where projections from some of the PMC areas traverse in an uninterrupted bar-like manner, the dorsum of this structure from the posteriormost nuclei to its rostralmost tip. All PMC regions also receive projections from the claustrum and the basal forebrain and project to the caudate, the basis pontis, and the zona incerta.

Pathology of the insular cortex in Alzheimer disease depends on cortical architecture.

The insular cortex plays important roles in a variety of regulatory mechanisms ranging from visceral control and sensation to covert judgments regarding inner well-being. The dementia of Alzheimer disease (AD) often includes behavioral dyscontrol and visceral dysfunction not observed in other diseases affecting cognition. This could be related to autonomic instability and to loss of the sense of self, and pathologic changes within the insula may play essential roles.

The limbic lobe and its output channels: implications for emotional functions and adaptive behavior.

Current dissatisfaction with the limbic system concept reflects a desire to move beyond the limbic system in efforts to explain key facets of emotional functions and motivational behavior. This review promotes an anatomical viewpoint, which originated as a result of histotechnical advances. These improvements paved the way for anatomical discoveries, which in turn led to the concepts of the ventral striatopallidal system and extended amygdala.

Phosphorylation of tau by fyn: implications for Alzheimer's disease.

The abnormal phosphorylation of tau protein on serines and threonines is a hallmark characteristic of the neurofibrillary tangles of Alzheimer's disease (AD). The discovery that tau could be phosphorylated on tyrosine and evidence that Abeta signal transduction involved tyrosine phosphorylation led us to question whether tyrosine phosphorylation of tau occurred during the neurodegenerative process. In this study we determined that human tau tyr18 was phosphorylated by the src family tyrosine kinase fyn.

Topography, cytoarchitecture, and cellular phenotypes of cortical areas that form the cingulo-parahippocampal isthmus and adjoining retrocalcarine areas in the monkey.

The monkey cingulo-parahippocampal isthmus was identified recently in the depths and lateral bank of the anterior calcarine fissure but was not characterized fully. Cytoarchitectonic and immunohistochemical results presented here reveal that the isthmus is composed of four cortical areas. These include the presubiculum of the isthmus (PrSi), parasubiculum of the isthmus (PaSi), area 29 of the isthmus (area 29i) and area prostriata (Pro), which has anterior (Pro-a) and posterior (Pro-p) divisions.

Prefrontal cortex in humans and apes: a comparative study of area 10.

Area 10 is one of the cortical areas of the frontal lobe involved in higher cognitive functions such as the undertaking of initiatives and the planning of future actions. It is known to form the frontal pole of the macaque and human brain, but its presence and organization in the great and lesser apes remain unclear. It is here documented that area 10 also forms the frontal pole of chimpanzee, bonobo, orangutan, and gibbon brains.

The selective vulnerability of brainstem nuclei to Alzheimer's disease.

In a study of thioflavin S-stained serial sections from the entire brainstem, we found that the inferior and superior colliculi and the autonomic, monoaminergic, cholinergic, and classical reticular nuclei were affected with varying degrees of severity and frequencies in 32 patients with Alzheimer's disease, whereas no changes were seen in the brainstems of 26 control subjects. The majority of the affected nuclei in patients with Alzheimer's disease exhibit either neurofibrillary tangles or senile plaques, and only a few display both. However, when sections were immunostained with the antibodies 10D5 and AT8 or ALZ50, both beta-amyloid and hyperphosphorylated epitopes of tau protein were found to be present in various concentrations in all the affected nuclei.

Selective pathological changes of the periaqueductal gray matter in Alzheimer's disease.

The periaqueductal gray matter (PAG) is a major neuroanatomical component of the brainstem and has pivotal roles in autonomic functions, behavior, and cognition, most notably in the processing of emotions and feelings. In a study of 32 brains obtained from patients with Alzheimer's disease (AD), thioflavin S-stained sections from the PAG contained major pathological changes in 81% of cases. These changes were absent in all 26 control brains (13 from normal subjects and 13 from non-AD patients).

Inferior parietal lobule projections to the presubiculum and neighboring ventromedial temporal cortical areas.

The entorhinal and perirhinal cortices have long been accorded a special role in the communications between neocortical areas and the hippocampal formation. Less attention has been paid to the presubiculum, which, however, is also a component of the parahippocampal gyrus, receives dense inputs from several cortical areas, and itself is a major source of connections to the entorhinal cortex (EC). In part of a closer investigation of corticohippocampal systems, the authors applied single-axon analysis to the connections from the inferior parietal lobule (IPL) to the presubiculum.

The parahippocampal gyrus in Alzheimer's disease. Clinical and preclinical neuroanatomical correlates.

The human parahippocampal gyrus forms a large part of the limbic lobe along the ventromedial part of the temporal cortical mantle. It is a variable and complicated cortex in terms of structure, and the latter is aggravated further by interfaces with the anterior insula anteriorly and the cingulate gyrus and occipital lobe posteriorly. Additional complications relate to its lateral border with the temporal cortex and especially the sulcal configurations that define this junction.

Orbitofrontal cortex pathology in Alzheimer's disease.

The orbitofrontal cortex has been examined in Alzheimer's disease (AD) from the viewpoint of neurofibrillary tangle (NFT) pathology, its laminar distribution and topography. NFT pathology in the orbitofrontal cortex is extensive in AD. In cases with extensive cortical pathology, NFTs extend from the pole of the frontal lobe to the orbitoinsular junction.

Localization of area prostriata and its projection to the cingulate motor cortex in the rhesus monkey.

Area prostriata is a poorly understood cortical area located in the anterior portion of the calcarine sulcus. It has attracted interest as a separate visual area and progenitor for the cortex of this modality. In this report we describe a direct projection from area prostriata to the rostral cingulate motor cortex (M3) that forms the fundus and lower bank of the anterior part of the cingulate sulcus.