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Biomedical subjects

A Diamond

Publications and source records attributed to A Diamond.

At least 37 records · Page 2Linked to original sources
PubMed1994

The relationship between cognition and action: performance of children 3 1/2-7 years old on a Stroop-like day-night test.

One hundred and sixty children 3 1/2-7 years of age (10 M, 10 F at each 6-month interval) were tested on a task that requires inhibitory control of action plus learning and remembering two rules. They were asked to say "day" whenever a black card with the moon and stars appeared and to say "night" when shown a white card with a bright sun. Children < 5 years had great difficulty. They started out performing well, but could not sustain this over the course of the 16-trial session. Response latency decreased from 3 1/2 to 4 1/2 years. Children < 4 1/2 years performed well when they took very long to respond. To test whether the requirement to learn and remember two rules alone was sufficient to cause children difficulty, 80 children 3 1/2-5 years old were tested on a control version of the task ("say 'day' to one abstract design and 'night' to another"). Even the youngest children performed at a high level. We conclude that the requirement to learn and remember two rules is not in itself sufficient to account for the poor performance of the younger children in the experimental condition.

Age Factors↗
PubMed1994

Young children's performance on a task sensitive to the memory functions of the medial temporal lobe in adults--the delayed nonmatching-to-sample task--reveals problems that are due to non-memory-related task demands.

Delayed nonmatching-to-sample performance was examined in children and found to be poor from 12 months until almost 2 years even at 5-s delay, although 5 s is well within such children's memory capacity. After 12 months of age, performance did not differ by delay (5 or 30 s). Because children's problems seemed largely unrelated to the task's memory demands, the 2 final studies explored the role of other cognitive abilities (deduction of an abstract rule, speed of processing, and resistance to interference or distraction). Telling children the rule or quadrupling sample presentation time had little effect. Because a salient stimulus (the reward) might interfere with keeping one's attention on the sample, the reward was omitted during initial sample presentation. This helped; at the 5-s delay, 15-month-olds performed at least as well as 21-month-olds in the basic condition, and 12-month-olds performed almost as well. Implications for the cognitive abilities improving during the 2nd year and for the functions of the medial temporal lobe are discussed.

Aptitude↗
PubMed1994

Phenylalanine levels of 6-10 mg/dl may not be as benign as once thought.

Results of a longitudinal study of children treated early and continuously for phenylketonuria (PKU) indicated that those children whose plasma phenylalanine (Phe) levels were approximately 3-5 times normal (6-10 mg/dl; levels previously considered safe in the US) were impaired in cognitive functions dependent on prefrontal cortex. In particular, the children had difficulty when required to hold information in the mind and, at the same time, exercise inhibitory control to resist doing what might be their first inclination. The deficits were evident in relation to each of several comparison groups and at all three age ranges (infants, toddlers and young children). The deficits appeared to be selective in that the same children who were impaired on the prefrontal cortex tests performed normally on the control tests. Since most of the control tasks tap functions dependent on parietal cortex or the medial temporal lobe, these results suggest that those functions are spared. To investigate the biological mechanism causing these cognitive deficits, we created an animal model of early-treated PKU. The results indicated that rats whose plasma Phe levels were mildly, but chronically, elevated had cognitive deficits (impaired performance on a behavioral task dependent on frontal cortex (delayed alternation)) and neurochemical changes (most notably, reduced dopamine metabolism in frontal cortex).

Animals↗
PubMed1994

An animal model of early-treated PKU.

Phenylketonuria (PKU) is a genetic disorder in which the hydroxylation of phenylalanine (Phe) to tyrosine is severely disrupted. If PKU is left untreated, severe mental retardation results. The accepted treatment is to restrict dietary intake of Phe. It has generally been thought that cognitive impairments are prevented if levels of Phe in plasma are maintained at or below five times the normal level. However, we recently documented that children treated early and continuously for PKU or children mildly hyperphenylalaninemic, who have levels of Phe in plasma approximately three to five times normal, still have cognitive impairments. These impairments are specific to the functions of frontal cortex (A. Diamond, W. Hurwitz, E. Lee, W. Grover, and C. Minarcik, unpublished observations). To investigate the mechanism underlying these cognitive deficits, an animal model of this condition was developed and characterized. Thirty-six rat pups were divided into three groups. The first group was treated pre- and postnatally with Phe and alpha-methylphenylalanine (a phenylalanine hydroxylase inhibitor). The second group was injected postnatally with Phe and alpha-methylphenylalanine. The third group received postnatal control injections. The mild plasma Phe elevations in the two experimental groups produced significant behavioral and neurochemical effects. Both experimental groups were impaired on a task dependent on frontal cortex, delayed alternation. Levels of dopamine, homovanillic acid (HVA), norepinephrine, and 5-hydroxyindole acetic acid (5-HIAA) were measured in medial prefrontal cortex, anterior cingulate cortex, striatum, and nucleus accumbens. The largest neurochemical reductions observed were in HVA and were in the two frontal cortical areas (medial prefrontal cortex and anterior cingulate cortex). There were modest reductions in HVA in the nucleus accumbens but no significant changes in HVA, or in any other metabolite or neurotransmitter, in the striatum. The levels of 5-HIAA were also reduced in all brain regions examined. There was no effect on norepinephrine in any of the four regions examined. Reduced levels of HVA in medial prefrontal cortex were the only neurochemical effect that significantly correlated with every measure of performance on the delayed alternation task. This study provides evidence of deleterious effects from mild elevations in the levels of Phe in plasma previously considered small enough to be safe. These effects include impaired performance on a cognitive task dependent on frontal cortex and reduced HVA levels in frontal cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Rate of maturation of the hippocampus and the developmental progression of children's performance on the delayed non-matching to sample and visual paired comparison tasks.

Although it has been widely speculated that the hippocampus, and the type of memory dependent upon the hippocampus, develops late in primates just as it does in rats (e.g., Nadel & Zola-Morgan, 1984; Bachevalier & Mishkin, 1984; Schacter & Moscovitch, 1984), the evidence to date would not seem to support this. Instead, there is behavioral evidence of very early recognition memory and anatomical evidence of very early hippocampal maturation in human and non-human primates. It is true, however, that the standard delayed non-matching to sample task, which requires recognition memory, is not mastered until quite late. The reason for this late mastery would appear to be the late emergence of some other ability required for the task, not recognition memory. The candidates for what that ability might be are (1) the capacity to plan and execute an indirect, two-action sequence, (2) the capacity to understand that the object stands for the reward, but is not the reward itself, (3) the ability to deduce an abstract rule, (4) the ability to make explicit on testing what can be shown implicitly during play, (5) the ability to quickly encode visual stimuli (speed of encoding), and (6) the ability to resist interference. Only empirical work will enable us to decide among these candidate abilities; that work is currently underway.

Animals↗
PubMed1989

The performance of human infants on a measure of frontal cortex function, the delayed response task.

The Delayed Response task is the best-established marker of frontal lobe function in nonhuman primates. This article reports the developmental progression of human infants on that task. It is proposed that maturation of prefrontal cortex may make possible these age-related improvements in Delayed Response performance. This would suggest the importance of prefrontal cortex functioning very early in life. Twelve infants (6 male, 6 female) were tested longitudinally every two weeks from 6-12 months of age. Another 36 infants (18 male, 18 female) were tested only once: 12 each at 8, 10, and 12 months. We predicted that infants would improve on Delayed Response over these ages because infants' performance on AB improves during this time, and Delayed Response is very similar to AB. The AB task, devised by Piaget, is used to study cognitive development in infants. The ages over which AB performance improves are well established. In both AB and Delayed Response, the subject watches as the experimenter hides a desired object in one of two identical wells. After a brief delay, the subject is allowed to reach. In AB, the object is hidden in the same well on subsequent trials until the subject reaches to the correct well; then side of hiding is reversed and the procedure repeated. In Delayed Response, side of hiding is varied randomly over trials. In the present study of Delayed Response each testing session consisted of 16 trials (eight to the right, eight to the left). We found: (1) the developmental progression for Delayed Response is almost identical to that for AB. (2) Infants of 7 1/2-9 months fail Delayed Response under the same conditions and in the same ways as do monkeys with lesions of dorsolateral prefrontal cortex. It is therefore suggested that AB and Delayed Response require the same cognitive abilities, and that improved performance on these tasks provides an index of maturation of frontal cortex function.

Attention↗
PubMed1989

Comparison of human infants and rhesus monkeys on Piaget's AB task: evidence for dependence on dorsolateral prefrontal cortex.

This paper reports evidence linking dorsolateral prefrontal cortex with one of the cognitive abilities that emerge between 7.5-12 months in the human infant. The task used was Piaget's Stage IV Object Permanence Test, known as AB (pronounced "A not B"). The AB task was administered (a) to human infants who were followed longitudinally and (b) to intact and operated adult rhesus monkeys with bilateral prefrontal and parietal lesions. Human infants displayed a clear developmental progression in AB performance, i.e., the length of delay required to elicit the AB error pattern increased from 2-5 s at 7.5-9 months to over 10 s at 12 months of age. Monkeys with bilateral ablations of dorsolateral prefrontal cortex performed on the AB task as did human infants of 7.5-9 months; i.e., they showed the AB error pattern at delays of 2-5 s and chance performance at 10 s. Unoperated and parietally operated monkeys succeeded at delays of 2, 5, and 10 s; as did 12 month old human infants. AB bears a striking resemblance to Delayed Response, the classic test for dorsolateral prefrontal function in the rhesus monkey, and indeed performance on AB and Delayed Response in the same animals in the present study was fully comparable. These findings provide direct evidence that AB performance depends upon dorsolateral prefrontal cortex in rhesus monkeys and indicates that maturation of dorsolateral prefrontal cortex may underlie the developmental improvement in AB performance of human infants from 7.5-12 months of age. This improvement marks the development of the ability to hold a goal in mind in the absence of external cues, and to use that remembered goal to guide behavior despite the pull of previous reinforcement to act otherwise. This confers flexibility and freedom to choose and control what one does.

Aging↗
PubMed1989

Successful performance by monkeys with lesions of the hippocampal formation on AB and object retrieval, two tasks that mark developmental changes in human infants.

In this study, (a) what determines success or failure on the AB and object retrieval tasks and (b) the relation between brain maturation and cognitive development as indexed by these tasks were examined. Specifically, does improved performance on these tasks with age reflect maturation of memory functions dependent on the medial temporal lobe? In AB, the S watches a reward being hidden in 1 of 2 wells; after a brief delay S reaches for that reward. The AB error consists of the S continuing to reach to the first location (A) when side of hiding is shifted to the second location (B). In object retrieval, a reward is placed in a transparent box open on 1 side. Although the reward is visible through all sides of the box, it can only be retrieved through the 1 open side. Intact cynomolgus monkeys and those with bilateral lesions of the hippocampal formation (H+) were tested. Although H+ monkeys exhibited impaired memory by performing poorly on the delayed nonmatching to sample taks, they performed well on AB at delays of 2-15 s. Performance declined as delays increased to 30 s, but H+ monkeys never showed the AB error pattern. On object retrieval, H+ monkeys succeeded quickly and efficiently, even when required to detour to the box opening. This reseach demonstrates that memory impairment alone cannot account for deficits on AB or on object retrieval and strengthens the conclusion (Diamond, 1988a, 1988b, in press) that improved performance on AB and object retrieval during infancy reflects maturation of dorsolateral prefrontal cortex.

Aging↗
PubMed1989

The morbidity and benefits of concurrent gracilis myocutaneous graft with pelvic exenteration.

This study was undertaken to evaluate the morbidity and potential benefits of concurrent gracilis myocutaneous graft with exenteration. All patients undergoing exenteration from 1962-1986 were reviewed, of whom 24 had concurrent grafts. The mean operative time, blood loss, and hospital stay were not different in patients with versus without grafts. The rate of fistula formation in the hospital was less in the graft group (P = .004) but was not different when compared with contemporary patients only. The total infection rate (wound and pelvic) was decreased in the graft group (P = .04) when graft infections were excluded. The major problem with the graft was significant necrosis of the flap(s) in nine of the 24 patients. There were no life-threatening complications attributed to concurrent placement of gracilis myocutaneous flaps. Experience with the technique is improving the cosmetic and functional outcome of the neovagina formed with the graft. Patients most likely to benefit from this procedure include those requiring immediate reconstruction or those with potentially poor healing due to high-dose pelvic radiation, including intraoperative radiation.

Female↗
PubMed1988

Some retinoblastomas, osteosarcomas, and soft tissue sarcomas may share a common etiology.

DNA and RNA were extracted from primary human osteosarcomas and soft tissue sarcomas obtained from patients without retinoblastoma and were analyzed by hybridization with a cDNA probe for RB mRNA; absence or alterations of the RB gene are associated with development of retinoblastoma. Most of the osteosarcomas or soft tissue sarcomas examined by us did not express detectable levels of RB mRNA, whereas normal cells and epithelial tumor cells did. One osteosarcoma expressed a 2.4-kilobase transcript in addition to a normal 4.7-kilobase species. Our data suggest that transcriptional inactivation or post-transcriptional down-regulation of the RB gene may be important in the etiology of some osteosarcomas and soft tissue sarcomas as well as retinoblastomas.

Bone Neoplasms↗
PubMed1988

Abilities and neural mechanisms underlying AB performance.

Schacter, Moscovitch, Tulving, McLachlan, and Freedman propose that infants may make the AB error because of immaturity of the memory system damaged in amnesia (e.g., the hippocampus). They contrast this with the proposal that infants may make the AB error because of immaturity of the frontal lobe system (Diamond; Diamond & Goldman-Rakic). Schacter et al.'s choice of subjects, however, did not permit a test of these 2 proposals, and characteristics of their task, such as length of delay, make comparison with infants difficult. Schacter et al. discuss sensitivity to proactive interference as a possible explanation for the AB error, but sensitivity to PI is more closely associated with frontal lobe damage than with amnesia. Schacter et al. associate perseveration with immaturity or damage to the frontal lobe; it is suggested here that this is better characterized as lack of inhibitory control. Tasks that are most likely to require frontal cortex function are those that demand both short-term memory and inhibitory control. AB is an excellent example of such a task.

Amnesia↗
PubMed1987

Esophageal zinc content in human squamous esophageal cancer.

Zinc and vitamin A are known to interact, and deficiencies have been associated with carcinogenesis in experimental animals and humans. Since we previously have demonstrated decreased plasma zinc and vitamin A levels in patients with esophageal cancer, we wished to examine endoscopically obtained epithelial tissue for vitamin A and zinc content. This was not feasible for vitamin A, but using newly developed techniques for zinc analysis of small tissue samples, we measured esophageal epithelial zinc as well as plasma zinc and plasma vitamin A in 21 patients with esophageal cancer, 17 patients with esophagitis, and 12 normals. Mean plasma zinc in the esophageal cancer group (56 +/- 3 micrograms/dl) (mean +/- SEM) was significantly less than in the esophagitis group (72 +/- 5 micrograms/dl) and the normals (78 +/- 5 micrograms/dl). Mean plasma vitamin A in the esophageal cancer group (32 +/- 3 micrograms/dl) was significantly less than the esophagitis group (57 +/- 4 micrograms/dl) or the normals (58 +/- 5 micrograms/dl). There was no significant difference in tissue zinc content (measured as micrograms zinc/g wet weight of tissue, mean +/- SEM) among cancerous tissue (57 +/- 5 micrograms/g) and adjacent normal tissue (61 +/- 4 micrograms/g), esophagitis tissue (66 +/- 6 micrograms/g) and adjacent normal tissue (61 +/- 6 micrograms/g), or normal esophageal tissue (59 +/- 6 micrograms/g). We conclude that deficiencies of zinc or vitamin A may be cofactors in the induction of human esophageal cancer, but a mechanism cannot be accounted for by differences in epithelial zinc content.

Carcinoma, Squamous Cell↗