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P S Goldman-Rakic

Publications and source records attributed to P S Goldman-Rakic.

At least 19 recordsLinked to original sources
PubMed1992

Acetylcholinesterase reactivity in the frontal cortex of human and monkey: contribution of AChE-rich pyramidal neurons.

Light and electron microscopic histochemistry were used to analyze the distribution of the enzyme acetylcholinesterase (AChE) in the frontal cortex of macaque monkey and human. In prefrontal, premotor, prelimbic, and medial paralimbic areas, AChE reactivity showed a characteristic bilaminar appearance due to a combination of positive neuronal and fiber labeling in deep layer III and layer V. In addition, layer I contained dense AChE-reactive fiber plexuses labeled throughout the frontal areas. One of the major issues addressed in this study was whether pyramidal neurons in the nonhuman primate cortex express AChE reactivity, as has been reported for humans. Three different histochemical methods were applied to provide confidence in the reliability of the results. Light microscopic analysis revealed strongly reactive, intensely stained pyramidal neurons in monkey as well as in the human. Further, these AChE-rich neurons exhibited the same pattern of laminar and regional variation in both species. In the prefrontal and premotor areas, AChE-rich pyramidal neurons predominated in layer III. In the motor cortex, they were also concentrated in layer III, but numerous AChE-rich pyramids were observed in layer V. In contrast, medial paralimbic areas had more AChE-rich neurons in layer V than in layer III. Finally, at the electron microscopic level, the subcellular distribution of AChE histochemical product in pyramidal neurons was identical in both monkey and human. The only difference noted between the two species was that the density of AChE-rich pyramidal neurons was greater in humans than in monkeys. Since nonhuman primates possess a system of AChE-reactive pyramidal neurons similar to human, they provide a potentially useful animal model for analyzing acetylcholinesterase neuronal systems in the cortex, which are compromised in various neuropathological diseases like Alzheimer's disease.

Acetylcholinesterase↗
PubMed1992

Light and electron microscopic characterization of dopamine-immunoreactive axons in human cerebral cortex.

The distribution and synaptic connections of dopamine axons were studied by light and electron microscopy in human cerebral cortex. For this purpose, dopamine immunoreactivity was characterized in apparently normal anteriolateral temporal cortex, which was removed to gain access to the medial temporal lobe during tumor excision or treatment of epilepsy. Nissl sections showed this to be granular neocortex. Dopamine fibers were distributed throughout this cortex, although there were relatively more fibers in layers I-II and in layers V-VIa, compared to layers III-IV and VIb, resulting in a bilaminar pattern of labeling. In all layers, fibers were seen to form numerous varicosities, and to vary in size from thick to very fine. Fibers were relatively straight, sparsely branched and were oriented in various planes within the cortex. However, in layer I, they often ran parallel to the pial surface. In order to analyze the functional interactions of dopamine fibers, individual cortical layers were surveyed for dopamine synapses. These were usually symmetrical (Gray's type II), although 13% of them were asymmetrical. Approximately 60% of dopamine synapses were made with dendritic spines, and 40% with dendritic shafts, and this ratio was similar in all layers. On both spines and shafts, it was common to see dopamine synapses closely apposed to an unlabeled asymmetric input, suggesting a dopamine modulation of excitatory input. Some postsynaptic dendritic shafts had features of pyramidal cells, including formation of spines. Since pyramidal cells are the major type of cortical spiny neuron, they probably represent the main target of dopamine synapses in this cortex. There were also dopamine profiles apposed to membrane densities on unlabeled axon terminals, suggesting another type of synaptic interaction. These findings provide the first documentation of dopamine synapses in the human cortex, and show that they form classical synaptic junctions. The location of these synapses on spines and distal dendrites, and their proximity to asymmetric synapses, suggest a modulatory role on excitatory input to pyramidal cells.

Axons↗
PubMed1992

The synaptology of parvalbumin-immunoreactive neurons in the primate prefrontal cortex.

Electron microscopy and immunocytochemistry with a monoclonal antibody against parvalbumin (PV) were combined to analyze the distribution and morphology of PV-immunoreactive (PV-IR) neurons and the synaptology of PV-IR processes in the principal sulcus of the macaque prefrontal cortex. Parvalbumin-IR neurons are present in layers II-VI of the macaque principal sulcus (Walker's area 46) and are concentrated in a band centered around layer IV. PV-IR cells are exclusively non-pyramidal in shape and are morphologically heterogeneous with soma sizes ranging from less than 10 microns to greater than 20 microns. Well-labeled neurons that could be classified on the basis of soma size and dendritic configuration resembled large basket and chandelier cells. A novel finding is that supragranular PV-IR neurons exhibit dendritic patterns with predominantly vertical orientations, whereas infragranular cells exhibit mostly horizontal or oblique dendritic orientations. PV-IR cells within layer IV exhibit a mixture of dendritic arrangements. Vertical rows of PV-IR puncta, 15-30 microns in length, resembling the "cartridges" of chandelier cell axons were most dense in layers II, superficial III, and the granular layer IV but were not observed in the infragranular layers. Cartridges were often present beneath unlabeled, presumed pyramidal cells. PV-IR puncta also formed pericellular nests around pyramidal cell somata and proximal dendrites, suggestive of basket cell innervation. PV-IR axons were occasionally observed in the white matter underlying the principal sulcus. Electron microscopic analysis revealed that PV-IR somata and dendrites are densely innervated by nonimmunoreactive terminals forming asymmetric (Gray type I) synapses as well as by fewer terminals forming symmetric (Gray type II) synapses. The majority of terminals forming symmetric synapses with PV-IR post-synaptic structures were not immunolabeled; however, some of these boutons did contain PV-immunoreactivity. PV-IR boutons exclusively form symmetric synapses and heavily innervate layer II/III pyramidal cells. PV-IR axon cartridges formed numerous axo-axonic synapses with the axon initial segments of pyramidal cells 15-20 microns beneath the axon hillock and also terminated on large axonal spines of the initial segment. Furthermore, we failed to observe a mixture of PV-immunoreactive and non-immunoreactive boutons composing a single axon cartridge. Pyramidal cell somata and proximal dendrites were also heavily innervated by PV-IR boutons forming symmetric synapses, again, consistent with basket cell innervation. In addition, PV-IR axon terminals frequently formed symmetric synapses with dendritic shafts and spines of unidentified neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1992

The anatomy of dopamine in monkey and human prefrontal cortex.

This chapter reviews recent evidence establishing the comparable organization of dopamine afferents and dopaminergic receptors in the human and monkey prefrontal cortex. Light microscopy using a dopamine-specific antibody reveals that the dopamine innervation in the human prefrontal cortex exhibits a distinct bilaminar distribution with dense bands of fibers in the upper and deeper strata of the cortex, closely resembling the patterning of dopamine fibers in the monkey prefrontal cortex. Also, EM-immunohistochemistry has now revealed identical synaptic complexes both in human and monkey. In both species, dopamine axons from symmetric synapses predominantly on the spines of pyramidal cells. In many cases, the same spine is apposed by an asymmetric, putatively excitatory synapse. Finally, both in human and monkey prefrontal cortex, the dopamine D1-specific ligand, 3H-SCH23390, and the D2-specific ligand, H3-raclopride, label binding sites in laminar positions which match the location of the densest dopamine innervation. These results indicate that the organization of the cortical dopamine system is essentially the same in macaque monkey and human and that the nonhuman primate is a suitable animal model for analysis of dopamine function in prefrontal cortex.

Afferent Pathways↗
PubMed1992

The prefrontal cortex and internally generated motor acts.

The neuroanatomical and neurophysiological data that have been obtained from experimental primates are converging on a framework for understanding the prefrontal influence on motor output. The framework isolates internally memory-based functions from externally guided sensory-based functions, identifies the internally-based functions with prefrontal circuits, the sensory-based functions with premotor circuits, and integrates the specializations of prefrontal, premotor and subcortical structures in the control of motor acts.

Animals↗
PubMed1991

Age-dependent decrease in the affinity of muscarinic M1 receptors in neocortex of rhesus monkeys.

In vitro autoradiography on tissue sections and receptor assay in cortical membrane homogenates revealed that pirenzepine high-affinity muscarinic sites (M1) decrease in affinity in the prefrontal cortex and in other cortical areas of aged rhesus monkey (Macaca mulatta). Carbachol competition experiments detected only a single, low-affinity class of sites in old monkeys, while two classes of sites (low and high affinity) were observed in young adults. The change in affinity in the aged monkeys is not accompanied by a decrease in the density of these sites and, further, the age-related decline in the affinity of the M1 site is reversible. In the presence of Mg2+, the M1 muscarinic receptors in the aged monkeys were capable of forming carbachol high-affinity sites. These results provide evidence for age-dependent functional changes in receptor activity in cerebral cortex and indicate that these receptors maintain a degree of plasticity that could be a strategic target for research aimed at treatment of memory disorders in aged humans.

Aging↗
PubMed1991

Synchronized overproduction of neurotransmitter receptors in diverse regions of the primate cerebral cortex.

A remarkable diversity of neurotransmitter receptors develops concurrently in disparate areas of the primate cerebral cortex. The density of dopaminergic, adrenergic, serotonergic, cholinergic, and GABAergic receptors (where GABA is gamma-aminobutyric acid) in rhesus monkey reaches a maximum level between 2 and 4 months of age and then declines gradually to adult levels in all layers of sensory, motor, and association regions. The synchronized development of neurotransmitter receptors in diverse layers and regions of the neocortex occurs pari passu with synaptogenesis, demonstrating unusual coordination of biochemical and structural maturation and supporting the hypothesis that the entire cerebral cortex matures as an integrated network, rather than as a system-by-system cascade.

Aging↗
PubMed1991

Myelo- and cytoarchitecture of the granular frontal cortex and surrounding regions in the strepsirhine primate Galago and the anthropoid primate Macaca.

As the first part of a comparative investigation of primate frontal cortex, we compared the frontal architectonic organization of Galago, a small-brained, strepsirhine (or "prosimian") primate, to that of an anthropoid primate, Macaca, by using myelin- and Nissl-stained material. We were able to distinguish many more areas in both taxa than have been recognized in most previous studies of the primate frontal lobe. In particular, we were able to subdivide many of the areas shown in the commonly cited architectonic map of Walker (J. Comp. Neurol. 73:59-86, 1940). Delineation of areas was greatly facilitated by the use of the Gallyas technique for staining myelin. The areal organization of much of frontal cortex (specifically, the premotor, orbital, and medial regions) appears to be very similar in Galago and Macaca. In these regions, we were able to recognize the same complement of areas in both taxa, with few exceptions. In the granular frontal cortex (GFC), by contrast, we were able to distinguish about twice as many areas in Macaca as in Galago. For most of the GFC areas of Galago, there are architectonically similar areas in Macaca; the areas shared by both taxa correspond mainly to the arcuate and superior areas of Macaca (i.e., the region encompassed by Walker's areas 45, 8A, and 8B). However, there are many additional, more rostral, areas in Macaca for which there are no obvious homologues in Galago. In particular, Galago lacks cortex resembling the distinctive, lightly myelinated cortex of the Macaca principal sulcus (Walker's area 46 and its subdivisions). Our results are difficult to reconcile with the view that frontal lobe organization varies little across taxa. Rather, they suggest that granular frontal cortex underwent considerable change during primate evolution, including the addition of new areas in anthropoids.

Animals↗
PubMed1991

Architectonics of the parietal and temporal association cortex in the strepsirhine primate Galago compared to the anthropoid primate Macaca.

A number of higher order association areas have been described in the parietal and temporal cortex of large-brained anthropoid primates such as Macaca. However, little is known about the evolution of these areas, and the existence of homologous areas has not yet been clearly demonstrated in other mammalian groups. We addressed this issue by comparing the myelo- and cytoarchitecture of posterior association cortex in the anthropoid Macaca to that of the small-brained, strepsirhine ("prosimian") primate Galago. Our results suggest that Galago possesses many, if not most, of the areas present in Macaca. We were able to identify regions in Galago which resemble Macaca posterior parietal area 7, superior temporal polysensory cortex (ST), inferotemporal visual cortex (IT), the temporoparietal auditory area (Tpt), and posterior parahippocampal cortex (areas TH and TF). Area 7, ST, and IT can each be subdivided further in Macaca, and for most of these subdivisions we were able to identify counterparts in Galago. However, we could not distinguish as many divisions of ST cortex in Galago as in Macaca, and it is possible that new areas arose in this region during anthropoid evolution. There also appear to be general differences in architectonic organization between these animals, with Macaca exhibiting greater development of pyramidal layer IIIc and of the internal granular layer (IV) across much of the parieto-temporal cortex. These findings suggest that many, although possibly not all, of the parietal and temporal association areas present in the modern anthropoid Macaca evolved early in primate history, prior to the divergence of the lineages leading to strepsirhines and anthropoids.

Animals↗
PubMed1991

Ipsilateral cortical connections of granular frontal cortex in the strepsirhine primate Galago, with comparative comments on anthropoid primates.

Modern studies of granular frontal cortex (GFC) in large-brained, anthropoid primates, such as Macaca, indicate that this region is comprised of many areal subdivisions. These areas vary in their architectonic appearance and each has a distinctive, diverse set of corticocortical connections. The great extent of the GFC region in anthropoids, and its high degree of areal parcellation, suggest that some GFC areas may be specializations of anthropoids, not found in other mammals. To investigate this possibility, we studied the corticocortical connections of GFC in the relatively small-brained, strepsirhine primate Galago, with a series of eight tracer injections in the frontal cortex, and an additional eight injections of parietal and temporal cortex. Tracers used were wheat-germ agglutinin conjugated to horseradish peroxidase and tritiated amino acids. Our results indicate that Galago GFC has strong, reciprocal connections with the parietal area-7 complex and with higher-order temporal areas; there are additional connections with extrastriate visual cortex, parahippocampal, and cingulate areas, and frontal cortex. Thus GFC has an extremely diverse array of cortical connections in Galago, as in Macaca. However, we also found that the pattern of parietofrontal connections is simpler in Galago than in Macaca. Specifically, parietal areas project to fewer discrete zones within the GFC of Galago, consistent with the view that these animals have fewer GFC areas than Macaca. In addition, Galago GFC possesses connections that specifically resemble those of Macaca arcuate cortex, but lacks connectional patterns that are characteristic of principalis cortex. These results are in accord with our previous architectonic studies, which indicated that Galago does not possess homologues of principalis areas. We conclude that the arcuate areas are common elements of primate GFC organization, while the areas located within and adjacent to the principal sulcus are anthropoid specializations.

Animals↗
PubMed1991

Dual mode of corticothalamic synaptic termination in the mediodorsal nucleus of the rhesus monkey.

Electron microscopic autoradiography (EM-ARG) was used to assess the synaptic organization of corticothalamic terminals in the parvicellular division of the mediodorsal thalamic nucleus. Examination of the synaptic organization in unreacted tissue revealed several distinct synaptic types distributed among glomerular and nonglomerular regions of the neuropil. Within glomeruli, three presynaptic terminal classes were found. The majority of profiles (as many as eight to ten per glomerulus) were presynaptic dendrites (PSDs) forming symmetric synaptic contacts with a central dendrite, and occasionally with other PSDs. One or two large terminals densely packed with round vesicles (LR terminals) were also present in each glomerulus. This terminal class made multiple asymmetric contacts with the central dendrite, as well as with many PSDs within the glomerulus. Finally, small terminals with round vesicles (SR terminals) formed asymmetric synaptic junctions with PSDs in some glomeruli. PSDs and SR terminals were also found in the extraglomerular neuropil, although in different proportions than in the glomeruli. In the extraglomerular neuropil SR terminals were the most abundant terminal class and these terminals made synaptic contacts with dendrites of all sizes. PSDs were seen in considerably smaller numbers than in the glomeruli. Finally, the extraglomerular neuropil contained a moderate number of small to medium terminals that formed symmetric synaptic junctions (SF terminals) with cell bodies and dendrites of all sizes. Synaptic profiles related to corticothalamic inputs were identified by injecting the prefrontal cortex of two rhesus monkeys with 3H-leucine and -proline and analyzing the distribution and morphology of radiolabeled terminals. Quantitative analysis of the density of silver grains over different tissue compartments revealed a positive labeling index for two terminal classes: SR and LR terminals. Labeled SR terminals were concentrated in the extraglomerular neuropil and labeled LR terminals were found within glomeruli where they formed synaptic contact with the central dendrite, as well as with presynaptic dendrites of the glomerulus. In contrast to many other thalamic nuclei, cortical input to the mediodorsal nucleus arrives via two distinctive synaptic pathways, one terminating extraglomerularly and the other terminating within the synaptic glomeruli. The dual mode of corticothalamic terminations in the mediodorsal nucleus suggests a more potent and possibly different role for cortical input in the regulation of neuronal activity in this association nucleus than in sensory nuclei of the thalamus.

Animals↗
PubMed1991

Prenatal specification of callosal connections in rhesus monkey.

Anatomical tracing and quantitative techniques were used to examine the tempo and pattern of maturation for callosal projection neurons in the monkey prefrontal cortex (PFC) during fetal and postnatal development. Nineteen monkeys were injected with retrograde tracers (fluorescent dyes, horseradish peroxidase conjugated to wheat germ agglutinin [WGA-HRP] or HRP crystals) at various ages between embryonic day 82 (E82) and adulthood. The size of injection sites was varied in fetal, newborn, and adult cases. In adults, labeled neurons were found in greatest density in the homotopic cortex of the opposite hemisphere and considerable numbers were also observed in a constellation of heterotopic areas including the medial and lateral orbital cortex, the dorsomedial convexity, and the pregenual cortex. The majority of labeled neurons were consistently concentrated in the lower half of layer III in all areas. In cases with large injection sites, callosal neurons of layer III formed a continuous and uninterrupted band that extended over the entire lateral surface of the prefrontal cortex spanning both homotopic and heterotopic areas. In contrast, in cases with small injection sites, the labeling of layer III neurons exhibited discontinuities. Between embryonic ages E82 and E89, injections limited to the cortical layers labeled only a small number of neurons in the opposite hemisphere, indicating that few callosal axons have invaded the cortex by this age. However, by E111 comparable injections labeled a large number of callosal neurons and many features of their distribution were adult-like. The number and constellation of cytoarchitectonic areas that were labeled in the frontal cortex of the opposite hemisphere were the same as in adults and the majority of callosal neurons were found in supragranular layer III. Finally, in fetal animals beyond E111, labeled neurons extended as a nearly unbroken band over a wide expanse of the dorsolateral PFC, resembling the pattern seen in adult monkeys with large injections. The conclusion we draw from these results, together with our earlier findings (Schwartz and Goldman-Rakic: Nature 299:154, 1982), is that callosal neurons whose axons enter the cortical layers of the primate prefrontal cortex achieve their mature laminar and areal distribution prior to birth and do so largely by cumulative processes.

Aging↗
PubMed1991

D1 dopamine receptors in prefrontal cortex: involvement in working memory.

The prefrontal cortex is involved in the cognitive process of working memory. Local injections of SCH23390 and SCH39166, selective antagonists of the D1 dopamine receptor, into the prefrontal cortex of rhesus monkeys induced errors and increased latency in performance on an oculomotor task that required memory-guided saccades. The deficit was dose-dependent and sensitive to the duration of the delay period. These D1 antagonists had no effect on performance in a control task requiring visually guided saccades, indicating that sensory and motor functions were unaltered. Thus, D1 dopamine receptors play a selective role in the mnemonic, predictive functions of the primate prefrontal cortex.

Animals↗
PubMed1991

Early phenotype expression of cortical neurons: evidence that a subclass of migrating neurons have callosal axons.

The use of [3H]thymidine labeling in combination with various axonal transport tracers has revealed that a subset of migrating neurons in the fetal monkey cerebrum issue axons to the opposite cerebral hemisphere while still migrating to their final positions in the cortical plate. Other cortical neurons with the same "birthdate" (i.e., that underwent their last round of DNA synthesis on the same day) are not retrogradely labeled by tracer injections of the opposite hemisphere. These findings suggest that the cardinal distinction between projection and local circuit neurons may be specified in postmitotic neurons before they acquire their final positions in the cortex.

Animals↗
PubMed1991

Distribution of dopaminergic receptors in the primate cerebral cortex: quantitative autoradiographic analysis using [3H]raclopride, [3H]spiperone and [3H]SCH23390.

A widespread distribution of dopamine D1 receptors in the neocortex is well recognized. However, the presence of dopamine D2 receptors in this structure has only recently been established [Martres et al. (1985) Eur. J. Pharmac. 118, 211-219; Lidow et al. (1989) Proc. natn. Acad. Sci. U.S.A. 86, 6412-6416]. In the present paper, a highly specific antagonist, [3H]raclopride, was used for autoradiographic determination of the distribution of D2 receptors in 12 cytoarchitectonic areas of the frontal, parietal, and occipital lobes of the rhesus monkey. A low density of D2-specific [3H]raclopride binding (1.5-4.0 fmol/mg tissue) was detected in all layers of all cortical areas studied. Throughout the entire cortex, the highest density of binding was consistently found in layer V. This is a unique distribution not observed so far for any other neurotransmitter receptor subtype in monkey cerebral cortex, including D1 receptor. In addition, a comparison was made of the distribution of [3H]raclopride and [3H]spiperone, which has been commonly used in previous attempts to label cortical D2 receptors. We found marked differences in the distribution of these two radioligands. In the prefrontal cortex, the pattern of [3H]spiperone binding in the presence of ketanserin resembled the combined distribution of 5-HT1C serotoninergic and alpha 2-adrenergic sites as well as D2 receptors. Thus, [3H]raclopride provides a better estimation of the D2 receptor distribution than does [3H]spiperone. The distribution of D2-specific binding of [3H]raclopride was also compared with the D1-specific binding of [3H]SCH23390 in the presence of mianserin to block labeling to 5-HT2 and 5-HT1C sites. The density of D1-specific [3H]SCH23390 binding was 10-20 times higher than that of D2-specific [3H]raclopride binding throughout the cortex. The densities of both [3H]raclopride and [3H]SCH23390 binding sites display a rostral-caudal gradient with the highest concentrations in prefrontal and the lowest concentrations in the occipital cortex. However, the binding sites of these two ligands had different laminar distributions in all areas examined. In contrast to preferential [3H]raclopride binding in layer V, a bilaminar pattern of [3H]SCH23390 labeling was observed in most cytoarchitectonic areas, with the highest concentrations in supragranular layers I, II and IIIa and infragranular layers V and VI. Whereas [3H]raclopride binding was similar in all cytoarchitectonic areas, [3H]SCH23390 exhibited some region-specific variations in the primary visual and motor cortex. The different regional and laminar distributions of D1 and D2 dopaminergic receptors indicates that they may subserve different aspects of dopamine function in the cerebral cortex.

Animals↗
PubMed1991

Topographic segregation of corticostriatal projections from posterior parietal subdivisions in the macaque monkey.

The distribution of corticostriatal projections from areas 7m, 7a, 7b and 7ip of the posterior parietal cortex was studied in rhesus monkeys using horseradish peroxidase conjugated with wheat-germ agglutinin as an anterograde tracer. All parietal subdivisions project bilaterally over a broad anteroposterior expanse of the caudate nucleus and putamen; however, the zones of densest terminal labeling varied for each parietal subdivision. Thus, area 7m projects preferentially to dorsal and dorsolateral portions of the head and anterior part of the body of the caudate nucleus. The main striatal target of area 7a is also in the head and anterior portion of the body of the caudate nucleus, but at dorsal and dorsomedial zones. The preferential target region of area 7ip in the striatum is in the posterior two-thirds of the body of the caudate nucleus, where the labeled terminals spare only the medial border. In contrast to the other parietal subdivisions, 7b projects preferentially to the putamen. In this nucleus, the location of labeling after 7b injections appears to correspond to the zones containing the representations of the distal forelimb and head. Each parietal subdivision projects to a rather extended anteroposterior domain in the contralateral neostriatum, the projection zones being always less extensive than in the ipsilateral side, but with a similar topographic distribution. Because we have shown previously that each parietal subdivision is part of a distinct distributed corticocortical network, the neostriatal territories innervated by each subdivision can be correlated with the corresponding network, thus providing insight into the functional specializations of the striatum.

Animals↗
PubMed1991

Commentary: the acquisition and use of human brain tissue in neuropsychiatric research.

Witelson and McCulloch (1991) report on the establishment of a collection of normal human brain tissue that was secured through a unique method of premortem and postmortem assessments. Their work highlights the growing need in neuro-scientific research for carefully characterized collections of human brain tissue from both normal control subjects and patients with specific neuropsychiatric disorders. Brain tissue of this type, however, has not been readily available. Patients with mental disorders may not be competent to consent to a postmortem brain donation; other obstacles include various socioeconomic and legal impediments to autopsies. In addition, a number of methodologic issues exist regarding human brain tissue collections, including the problem of standardized postmortem diagnostic assessment and difficulty in establishing uniform procedures for processing formalin-fixed and frozen tissue. Various proposals to enhance brain-tissue collections are discussed. These include the establishment of networks for tissue donation and use, the linking of ultimate postmortem brain tissue collection to prospective clinical studies, and promulgation of standardized procedures for methods of postmortem diagnosis and tissue handling.

Adult↗