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Biomedical subjects

P S Goldman

Publications and source records attributed to P S Goldman.

18 recordsLinked to original sources
PubMed1979

Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex of rhesus monkey.

Depletion of dopamine in a circumscribed area of association cortex in rhesus monkeys produces an impairment in spatial delayed alternation performance nearly as severe as that caused by surgical ablation of the same area. This behavioral deficit can be pharmacologically reversed with dopamine agonists such as L-dopa and apomorphine. These data provide direct evidence that dopamine plays an important role in a specific cortical function.

Animals↗
PubMed1979

Regional distribution of monoamines in the cerebral cortex and subcortical structures of the rhesus monkey: concentrations and in vivo synthesis rates.

Endogenous monoamine concentrations and turnover rates vary markedly in different regions of neocortex as well as in various subcortical structures of young adult rhesus monkeys. Monoamine levels and synthesis rates in amygdala, hippocampus, neostriatum, thalamus and brain stem are generally similar to comparable measures previously reported in a variety of species. However, extending and confirming the results of an earlier study, cortical monoamines exhibit topographically specific patterns of distribution. Thus, dopamine concentration is highest in the prefrontal and temporal neocortex; it decreases along the fronto-occipital axis and only trace amounts are detectable in the visual cortex. The distribution of norepinephrine is similar to that of dopamine except that the highest concentrations of norepinephrine are found in somatosensory cortex instead of prefrontal cortex. The pattern of distribution of serotonin is more uniform. However, the distribution of its metabolite, 5-hydroxyindoleacetic acid, is complementary to that of dopamine: the concentration is lowest in prefrontal cortex and highest in posterior regions of the telencephalon. Synthesis of catecholamines as measured by DOPA accumulation in monkeys treated with an aromatic amino acid decarboxylase inhibitor, NSD 1015, generally parallels the distribution of the catecholamines while indoleamine synthesis, as measured by 5-HTP accumulation, is similar to the distribution of 5-hydroxyindoleacetic acid. It may be significant that synthesis rates for the catecholamines are especially high in various areas of association cortex.

Amygdala↗
PubMed1979

An improved method for embedding brain tissue in albumin-gelatin.

A new modification of the Snodgrass-Dorsey (1963) albumin embedding method is described. Formalin fixed brains of various ages of rhesus monkey (Macaca mulatta) were sunk in 10% phosphate buffered formalin which contained 30% sucrose, and then embedded in a 3% gelatin, 30% egg albumin solution which had been centrifuged to ensure uniformity. The albumin-gelatin was hardened in formaldehyde fumes and blocks cut frozen at 10-40 micron. Sections thus prepared can be handled easily and mounted without damage to the tissue. Modifications of conventional cell and fiber stains produce high quality finished slides in which the stained brain tissue is surrounded by a colorless albumin-gelatin matrix.

Animals↗
PubMed1978

Neuronal plasticity in primate telencephalon: anomalous projections induced by prenatal removal of frontal cortex.

When the dorsolateral prefrontal cortex in one hemisphere of a rhesus monkey is resected 6 weeks before birth and the fetus survives to postnatal ages, neurons of the corresponding cortex in the intact hemisphere issue a greatly expanded projection to the contralateral caudate nucleus in addition to a normal projection to the ipsilateral caudate. The enhancement of the crossed prefronto-caudate pathway after prenatal neurosurgery provides direct evidence for lesion-induced neuronal rearrangement in the primate telencephalon.

Animals↗
PubMed1978

Prenatal removal of frontal association cortex in the fetal rhesus monkey: anatomical and functional consequences in postnatal life.

Anatomical and behavioral consequences were examined following bilateral or unilateral resections of the presumptive dorsolateral prefrontal cortex in 4 rhesus monkey fetuses at E102 (102nd embryonic day), E104, E106 and E119, with subsequent replacement in utero and delivery at later stages of development. Unoperated monkeys of appropriate pre- and postnatal ages served as controls for certain features of morphogenesis and tectogenesis. Monkeys given comparable unilateral or bilateral lesions at selected postnatal ages were used as controls for the behavioral effects of prenatal resection as well as for neuropathological examination. The behavioral evaluation provided evidence for extraordinary preservation of function after frontal cortical resection in the prenatal period. During the entire course of its postnatal development, a monkey that sustained bilateral resection as a fetus at E106 performed surprisingly well and clearly with the competence of unoperated monkeys of identical or older ages on tasks selective for dorsolateral prefrontal cortical function; it did not exhibit deficits characteristic of animals that have comparable or even smaller resections as juveniles or adults. Following either unilateral or bilateral resection prior to E106, ectopic sulci and gyri appeared in intact regions of the frontal lobe of each hemisphere, as well as in locations at a considerable distance from the lesions, such as the temporal and occipital lobes. The cytoarchitectonic characteristics of the cortex in these anomalous gyri were typical of adjacent cortex in the regions in which they appeared. Examination of the parvocellular subdivision of the mediodorsal thalamic nucleus yielded the novel finding that this principal source of essential projections to the dorsolateral prefrontal cortex contained a virtually normal number of neurons in postnatal monkeys, following unilateral or bilateral lesions performed at or before E106, and exhibited only a partial loss of neurons after surgery at E119. The same cells regularly degenerate following comparable resections in the postnatal period. The survival of these neurons in prenatally operated monkeys is unprecedented, and can be explained by several hypotheses, including the possibility that their axons become rerouted to their structures in the absence of their normal targets. The present results thus demonstrate that ablation of a circumscript area of the frontal cortex in a non-human primate a full two months before birth may leave the functions later to be subserved by that area unaffected. Such early surgical intervention results in significant alteration in the gross morphological characteristics of the cortex, and apparently induces a functionally compensatory reorganization of thalamocortical connections. Similar principles may account for sparing of function following early damage to the human brain.

Animals↗
PubMed1978

Functional development of the dorsolateral prefrontal cortex: an analysis utlizing reversible cryogenic depression.

The dorsolateral prefrontal cortex of rhesus monkeys was functionally inactivated by local hypothermia as the monkeys performed spatial delayed-response and spatial delayed-alternation tasks at different stages of postnatal development. Cryogenic depression of prefrontal cortex at a temperature sufficient to induce 21--25% decrements in delayed-response performance in 34--36-month-old-monkeys, produced deficits of only 7--8% in 19--31-month-old and no detectable loss in younger monkeys, 9--16 months of age. Delayed-alternation performance was impaired by local hypothermia as early as 8.5 months of age, but maximal cooling-induced deficits on this task were not observed before 33 months of age. Thermal gradients mapped in representative monkeys at different stages of development were remarkable similar, indicating that the age-dependent differences in behavior were not attributable to technical factors. The results obtained in the present study on normal developing monkeys confirm the interpretation of previous research on brain-damaged infants that functional maturation of the dorsolateral prefrontal cortex is protracted over several years of postnatal life, and extends the earlier studies by indicating that the lower limit for maturity of dorsolateral function is close to puberty in this species. Further, the present study revealed that delayed-response and delayed-alternation performance are dissociable dorsolateral functions which achieve maturity at different rates. The convergence of evidence from reversible neural depression and permanent lesion methods provides strong validation for neurobehavioral analysis as a general approach to the study of regional maturation of the brain.

Age Factors↗
PubMed1977

Columnar distribution of cortico-cortical fibers in the frontal association, limbic, and motor cortex of the developing rhesus monkey.

The terminal distribution of cortico-cortical connections was examined by autoradiography 7-8 days following injections of tritium labeled amino acids into the dorsal bank of the principal sulcus, the posterior part of the medial orbital gyrus, or the hand and arm area of the primary motor cortex in monkeys ranging in age from 4 days to 5.5 months. Labeled axons originating in these various regions of the frontal lobe have topographically diverse ipsilateral and contralateral destinations but virtually all of these projections share a common mode of distribution: they terminate in distinct vertically oriented columns, 200-500 mum wide, that extend across all layers of cortex and alternate in regular sequence with columns of comparable width in which grains do not exceed background. Spatial periodicity in the pattern of transported label in such regions as the prefrontal association cortex, the retrosplenial limbic cortex and the motor cortex indicates that columination in the intracortical distribution of afferent fibers is not unique to sensory specific cortex but is instead a general feature of neocortical organization. A columnar mode of distribution of cortico-cortical projections is present in monkeys at all ages investigated but is especially well delineated in the youngest of them. Thus, grain concentrations within columns are very high in monkeys injected at 4 days of age, somewhat lower in monkeys injected at 39-45 days of age, and least dense in those injected at 5.5 months. The distinctness of the spatially segregated pattern of innervation in the cortex of neonates indicates that the columnar organization of association-fiber systems in the frontal and limbic cortex is achieved before or shortly after birth.

Animals↗
PubMed1977

An intricately patterned prefronto-caudate projection in the rhesus monkey.

The distribution of prefronto-caudate fibers in the caudate nucleus was studied autoradiographically in monkeys of various ages in which tritiated amino acids had been injected into the middle one-third of the length of the dorsal bank of the principal sulcus. The results indicate that, contrary to previous reports which had suggested a projection to only the head of the caudate nucleus, area 9 of Brodmann projects to the entire length of the nucleus. In the head of the caudate nucleus the cortico-caudate fibers are distributed in a pattern which is remarkable in two respects. First, the grains are not uniformly distributed but rather are segregated into clusters separated from one another by territories in which grain density does not exceed background. Second, individual clusters of grains, circular or elliptical in shape, surround grain free cores. These patterns of fiber distribution within the head of the nucleus are more sharply defined in newborn than in older monkeys. Our findings suggest that the caudate nucleus is organized more as an anatomic and functional mosaic than as the homogeneously organized structure that it is commonly considered to be.

Afferent Pathways↗
PubMed1976

Postnatal maturation of subcortical projections from the prefrontal cortex in the rhesus monkey.

Orbital and dorsolateral prefrontal lesions were performed on a series of rhesus monkeys at 2, 6, or 24 months of age. The consequent degeneration in the efferent pathways from these cortical regions to the caudate nucleus, the dorsomedial nucleus of the thalamus and adjacent structures was studied at 5- and 15-day survival times by a modification of the Nauta-Gygax method for tracing degenerating fibers. Following dorsolateral lesions, considerable numbers of black-impregnated degenerating fibers were found in the parvocellular division of the dorsomedial nucleus and in the fiber bundles of the internal capsule and the subcallosal fasciculus at all ages.

Animals↗
PubMed1975

Age, sex, and experience as related to the neural basis of cognitive development.

Studies of rhesus monkeys raised from infancy without portions of the central nervous systems provide evidence regarding the timing of functional maturity of specific regions. Some findings have been presented which show that deficits following lesions of specific cortical areas emerge at that age when abilities dependent upon the cortical area in question take on adult form in unoperated monkeys. However, age is but a convenient abstraction for conditions that vary over time. One such condition is the presence and titer of gonadal hormones. The finding that orbital functions may develop at different times in males and females is of interest from a number of perspectives, but it is especially stimulating to consider the possibility that the development of cortical tissue may be regulated by neuroendocrine factors in a fashion analogous to that envisioned for differentiation of hypothalamic mechanisms. Finally, experiential factors may depend greatly on the maturational status of those brain regions designed to be recipients of that stimulation. The fact that young children acquire second languages with far greater ease than adults or conversely that language fails to develop before 18-28 months of age regardless of training are features of human experience consistent with the interdependence of experience and neurological maturation. The present finding that training at relatively early periods of development facilitated recovery from brain injury indicates further that brain-damaged individuals can be even more sensitive to the effects of previous experience than intact cases. Age, sex, and experience are factors that may be isolated for experimental purposes and for the purpose of discussion. However, it is precisely the complex interactions of these variables that constitute the subject matter of future research in neurobiology, to which studies of infant monkeys may contribute animal models of normal and disordered human development.

Age Factors↗