Gary W. Van Hoesen

Prosopagnosia: Anatomic basis and behavioral mechanisms

Critical analysis of postmortem and CT scan data indicates that prosopagnosia is associated with bilateral lesions of the central visual system. Those lesions are located in the mesial occipitotemporal region and are functionally symmetric.The prime factor in the appearance of prosopagnosia is the requirement to evoke the specific context of a given visual stimulus. The “ambiguity” of the stimulus (the frequency with which different members of a group are visually similar) is an adjuvant factor. But prosopagnosia is not specific to human faces. The phenomenon appears in relation to any visually “ambiguous” stimulus whose recognition depends on contextual memory evocation.

The parahippocampal gyrus: New observations regarding its cortical connections in the monkey

Abstract In the rhesus monkey, the cortices of the parahippocampal gyrus are pivotal relay areas in a series of multisynaptic input pathways that connect the hippocampal formation to other areas of the cerebral cortex. Recent investigations now suggest that they play a similar role in relaying hippocampal formation output back to widespread areas of the cerebral cortex and, in particular, to the association cortices.

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. Imaging techniques and stereological tools are used to characterize this area across species and provide preliminary estimates of its absolute and relative size. Area 10 has similar cytoarchitectonic features in the hominoid brain, but aspects of its organization vary slightly across species, including the relative width of its cortical layers and the space available for connections. The cortex forming the frontal pole of the gorilla appears highly specialized, while area 10 in the gibbon occupies only the orbital sector of the frontal pole. Area 10 in the human brain is larger relative to the rest of the brain than it is in the apes, and its supragranular layers have more space available for connections with other higher-order association areas. This suggests that the neural substrates supporting cognitive functions associated with this part of the cortex enlarged and became specialized during hominid evolution.

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 Alzheimers disease (AD). The discovery that tau could be phosphorylated on tyrosine and evidence that Aβ 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. By developing both polyclonal and monoclonal probes specific for phospho-tyr18, we found that the phosphorylation of tau at tyr18 occurred at early developmental stages in mouse but was absent in the adult. Our phosphospecific probes also revealed that paired helical filament preparations exhibited phospho-tyr18 reactivity that was sensitive to phosphotyrosine-specific protein phosphatase treatment. Moreover, immunocytochemical studies indicated that tyrosine phosphorylated tau was present in the neurofibrillary tangles in AD brain. However, the staining pattern excluded neuropil threads and dystrophic neurites indicating that tyrosine phosphorylated tau was distributed in AD brain in a manner dissimilar from other abnormally phosphorylated tau. We also found evidence suggesting that differentially phosphorylated tau existed within degenerating neurons. Our data add new support for a role for fyn in the neurodegenerative process.

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. These two systems, together with the basal nucleus of Meynert and the septum-diagonal band system, serve as output channels for an expanded version of the classic limbic lobe of Broca, which contains all non-isocortical parts of the cortical mantle together with the large laterobasal-cortical amygdaloid complex. Thus defined, the limbic lobe contains all of the major cortical (e.g. orbitofrontal, cingulate and insular cortices in addition to the hippocampal formation) and cortical-like (laterobasal-cortical amygdala) structures known to be especially important for emotional and motivational functions. In their role as output channels for the limbic lobe, the basal forebrain functional-anatomical systems contribute to the establishment of a number of cortico-subcortical circuits, which provide an important part of the anatomical substrate for the elaboration of emotional functions and adaptive behavior.

Connections of the Monkey Cingulate Cortex

Among several nineteenth century reports on the cortical convolution located above the corpus callosum, it was Burdach’s (1822) description that gave rise to the term cingulate gyrus. Early attempts to address the functional implications of the cingulate region were based primarily on limited neuro-anatomical observations and a host of gross comparative anatomical parallels. The most popular functional theory was formulated by Broca (1878), who suggested that the modality of olfaction was processed in a number of cerebral centers which included the anterior olfactory region, hippocampus, and cingulate gyrus. Collectively Broca termed these cerebral centers the grand lobe limbique. The cingulate gyrus was later shown to have extensive connections with the anterior thalamic nuclei (Clarke and Boggon, 1933).

The Hippocampal Formation of the Primate Brain

The long-standing interest of neuroscientists in the hippocampal formation has occurred from the perspective of two rather different points of view. On the one hand, the comparatively simple cytoarchitecture of the hippocampal formation and the laminar segregation of its extrinsic and intrinsic afferents make it an interesting and relatively simple model system for experimental manipulation and investigation. Chapter 8 in this volume, by Schwartzkroin and Mueller, is a thoughtful review of how effective the hippocampus has been as a model system for neurophysiological studies using the in vitro slice preparation. Other investigations have utilized the hippocampal formation to study the effects of genetic defects in neuronal development (e.g., Nowakowski and Davis, 1985), collateral sprouting induced by deafferentation (e.g., Lynch et al. 1972; Cotman and Nadler, 1978), or intracerebral transplantation (e.g., Frotscher and Zimmer, 1986). While most of the studies that use the hippocampal formation as a model system have focused on the rodent, the other major interest in the hippocampal formation has grown out of a variety of clinical and experimental data derived from humans and nonhuman primates. These latter investigations have focused on the disruption of certain aspects of the memory process produced by hippocampal lesions as first described in human neurosurgical patients (Scoville and Milner, 1957; Penfield and Milner, 1958) and subsequently investigated in nonhuman primates (e.g., Moss et al. 1981).

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. Moreover, the posterior cingulate areas are interconnected with the parahippocampal regions, whereas the medial parietal cortex projects only sparsely to the presubiculum. Although local interconnections and shared remote connections of all PMC components suggest a functional relationship among them, the distinct connections of each area with different neural structures suggests that distinct functional modules may be operating within the PMC. Our study provides a large-scale map of the PMC connections with the rest of the brain, which may serve as a useful tool for future studies of this cortical region and may contribute to elucidating its intriguing pattern of activity seen in recent functional imaging studies.

WGA-HRP as a transneuronal marker in the visual pathways of monkey and rat

Wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) was injected intraocularly in monkeys and rats. All known primary visual pathways were labeled and, in addition, ocular dominance columns in visual cortex were labeled in monkey, and in rat, parabigeminal, oculomotor, thalamic reticular, and visual cortical areas were labeled as well as neuronal soma in superior colliculus. We conclude that WGA-HRP is a useful transneuronal marker for visual pathways.

Corticopontine projections from the cingulate cortex in the rhesus monkey

The corticopontine projections of the cingulate cortices were investigated in the rhesus monkey with the use of autoradiography. A well-organized topography of projections was observed with anterior cingulate cortex projecting to the medial part of the pontine gray matter and posterior cingulate cortex projecting to the lateral part. Together these projections form a circle of termination around the periphery of the pontine gray matter.