Cognition and comportment are subserved by interconnected neural networks that allow high-level computational architectures including parallel distributed processing. Cognitive problems are not resolved by a sequential and hierarchical progression toward predetermined goals but instead by a simultaneous and interactive consideration of multiple possibilities and constraints until a satisfactory fit is achieved. The resultant texture of mental activity is characterized by almost infinite richness and flexibility. According to this model, complex behavior is mapped at the level of multifocal neural systems rather than specific anatomical sites, giving rise to brain-behavior relationships that are both localized and distributed. Each network contains anatomically addressed channels for transferring information content and chemically addressed pathways for modulating behavioral tone. This approach provides a blueprint for reexploring the neurological foundations of attention, language, memory, and frontal lobe function.

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The nucleus basalis (NB) of the human brain is a large, complex, and highly differentiated structure. Many of its neurons are magnocellular, hyperchromic, isodendritic, acetylcholinesterase-rich, and choline-acetyltransferase-positive. Concurrent histochemical and immunological staining demonstrated that all choline-acetyltransferase-positive NB neurons in the human brain also contain acetylcholinesterase enzyme activity. Only a small minority of acetylcholinesterase-rich magnocellular cell bodies in the NB failed to show choline acetyltransferase immunoreactivity. Sections that were counterstained for Nissl substance showed that 80-90% of all magnocellular neurons in the NB were choline-acetyltransferase-positive and therefore cholinergic. These characteristics, which are very similar to those of the NB in the monkey brain, justified the designation of these cholinergic neurons in the human brain as the Ch4 (or NB-Ch4) complex. On morphological grounds, the compact parts of the human NB-Ch4 complex were divided into distinct sectors which appeared to show a greater level of differentiation than in the monkey brain. In addition to the compact sectors, interstitial elements of NB Ch4 were embedded within adjacent fiber bundles. The putative cortical projections from NB-Ch4 were identified in the form of acetylcholinesterase-rich fibers. These fibers formed a dense plexus in all cortical regions but also displayed laminar and regional variations. Limbic and paralimbic areas had higher concentrations of these fibers than the immediately adjacent neocortical association areas. Alzheimer's disease was associated with a marked depletion of cortical acetylcholinesterase. Two cases of Alzheimer's disease with relatively selective NB-Ch4 cell loss supported the hypothesis that the corticopetal cholinergic pathways in the human brain may have a topographical organization similar to that in the monkey brain.

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The central sensory and motor connections of various respiratory, cardiovascular, aqd gastrointestinal viscera were analyzed using the transganglionic and retrograde transport of horseradish peroxidase (HRP).In 42 adult cats, we examined the brain stem and peripheral ganglia following microinjections of HRP (10 p1) into individual visceral organs-larynx, extrathoracic trachea, intrathoracic trachea, right main bronchus, right lung (upper lobe), heart, and stomach. Comparison of individual cases led to the conclusion that distinct patterns of sensory and motor projections to the medulla exist for each visceral organ studied.The nucleus of the tractus solitarius (nTS) receives the sensory projections from all the viscera listed above, with two exceptions: (1) a few sensory fibers from the larynx terminate in the ipsilateral spinal tract of the trigeminal nerve (spV), and (2) some sensory fibers from the bronchus, lung, and stomach terminate in the area postrema (ap). Within the nTS, the sensory fibers from each visceral organ terminate in a number of subnuclei. The dnTS, mnTS, and ncom receive sensory projections from all the viscera studied. The remaining five subnuclei (dlnTS, ni, nI, vlnTS, vnTS) of the nTS are not connected to all viscera, and the density of projections to these regions varies for different viscera. However, there does not seem to be any specific region of the medulla which is devoted entirely to receiving the sensory fibers from a particular visceral organ. Rather, the rostrocaudal extent of sensory fibers, from most of the viscera studied, spans the entire length of the medulla. Differences in the central representation of viscera were found to be subtle and to lie within the organization of the nuclear subgroups of the nTS. The central representation of unpaired or midline viscera (e.g., trachea and heart) is bilateral for both sensory and motor innervation. However, for unilateral, paired viscera (e.g., bronchi and lungs), it was consistently found that over one third of the sensory and motor representation is contralateral. Control experiments involving vascular injections of HRP excluded the possibility that this contralatera1 labeling could have been due to vascular uptake of the enzyme. The localization of sensory perikarya of visceral afferents in the "principal visceral ganglion" of the vagus-the nodose ganglion-was overlapping, and no well-demarcated regions in the nodose ganglion could be identified that received projections primarily from a given visceral organ.The motor nuclei providing parasympathetic (preganglionic) and somatic motor innervation to the viscera were primarily the dmnX, nA, and nRA. The entire dmnX (extending over 10-15 mm rostrocaudally), contributed fibers to each area injected with HRP, with the exception of the extrathoracic trachea. No region in the dmnX was found where preference was given to a specific viscus. The nA contributed efferents to all the viscera studied, and this contribution came from the 468M. KALIA AND M-M. MESULAM entire 6 mm of n...