A neural basis for general intelligence.

Universal positive correlations between different cognitive tests motivate the concept of "general intelligence" or Spearman's g. Here the neural basis for g is investigated by means of positron emission tomography. Spatial, verbal, and perceptuo-motor tasks with high-g involvement are compared with matched low-g control tasks. In contrast to the common view that g reflects a broad sample of major cognitive functions, high-g tasks do not show diffuse recruitment of multiple brain regions. Instead they are associated with selective recruitment of lateral frontal cortex in one or both hemispheres. Despite very different task content in the three high-g-low-g contrasts, lateral frontal recruitment is markedly similar in each case. Many previous experiments have shown these same frontal regions to be recruited by a broad range of different cognitive demands. The results suggest that "general intelligence" derives from a specific frontal system important in the control of diverse forms of behavior.

In vitro 3,5,3'-triiodothyronine binding to rat cerebrocortical neuronal and glial nuclei suggests the presence of binding sites unavailable in vivo.

The maximal binding capacity (MBC) of the rat cerebrocortical nuclear T3 receptor, as determined by in vivo saturation techniques, is approximately half that measured in vitro on isolated nuclei or solubilized receptors. To investigate this disparity, the MBC values determined in vivo and in vitro for both rat cerebral cortex and liver were compared, taking into account nuclear receptor loss or inactivation and the presence of endogenous T3. By Scatchard analysis of T3 binding to isolated nuclei in vitro at 37 C, the uncorrected MBC values (mean +/- SEM; n = 3) for the cerebrocortical nuclear T3 receptor in euthyroid and hypothyroid rats were 0.80 +/- 0.14 and 0.66 +/- 0.07 ng T3/mg DNA, respectively, and were not significantly different. The Kd values were also not significantly different (5.6 +/- 0.3 and 5.2 +/- 0.9 X 10(-10) M, respectively). After corrections for incomplete dissociation and receptor inactivation under the in vitro conditions, the overall mean MBC increased by approximately 33% to 0.97 ng T3/mg DNA, or about 3.6 times the in vivo MBC. In addition, cerebrocortical nuclei prelabeled in vivo with +/- 131I]T3 at near-saturating levels and subsequently incubated with [125I]T3 in vitro at concentrations up to 10 times the Kd were shown to bind as much as 4 times more T3 in vitro relative to the amount of endogenous hormone which dissociated, thus exceeding the in vivo MBC by a factor of two. Parallel experiments with isolated liver nuclei did not show the existence of nuclear T3 receptors which were available only in vitro, even when the corrected MBC (0.77 ng T3/mg DNA) was compared with the MBC obtained by the in vivo saturation technique (0.76 ng T3/mg DNA). The experiments with liver nuclei were done at 25 C to reduce the rate of inactivation or loss of nuclear T3 receptors in this tissue. By fractionating isolated cerebrocortical nuclei into neuronal and glial subpopulations on discontinuous sucrose gradients, the high affinity, limited capacity nuclear T3 receptor could only be identified in the neuronal fraction. No consistent specific binding of T3 was observed in glial nuclei that were 80% pure, suggesting that either glial cells in the adult rat are not likely to be direct targets of thyroid hormone or that thyroid hormone may act via nonnuclear receptor-mediated pathways. We conclude that only neurons have specific high affinity, limited capacity nuclear T3 receptors and that as many as half of these receptors may not be accessible to plasma T3.(ABSTRACT TRUNCATED AT 400 WORDS)

Studies of nuclear 3,5,3'-triiodothyronine binding in primary cultures of rat brain.

Primary cultures of enzymatically dispersed cells from 17-day-old fetal rat cerebral hemispheres were used to detect the presence of nuclear T3 receptors. Cells grown in Minimum Essential Medium supplemented with 10% fetal bovine serum were grown in parallel with cytosine-arabinoside (ARA-C)-treated counterparts which had been exposed to the antimetabolite for 18 h on culture days 3 and 5 or 4 and 6. Five days after the second ARA-C treatment, phase contrast photomicrographs showed substantial loss of the proliferating basal cells, corresponding to an 85% decrease in cell number. Immunocytochemical studies using antiglial fibrillary acidic protein (anti-GFAP) and antineurofilament (anti-NF) antisera demonstrated loss of GFAP-positive cells (astrocytes) and preservation of NF-positive cells (neurons), the latter considered to be a nondividing population under the culture conditions. Nuclei obtained from the brain cell cultures at this time by Triton washing bound T3 with properties similar to those observed in vivo. Scatchard analysis showed a single, high affinity, limited capacity nuclear T3 receptor with a maximal binding capacity (MBC) of 0.53 +/- 0.10 ng T3/mg DNA and a Kd of 0.19 +/- 0.02 nM (+/- SE; n = 4). ARA-C treatment resulted in a mean decrease in DNA per culture dish of 54%, with an accompanying 2-fold enrichment of the MBC, and no change in the Kd. In untreated cultures grown for 20 days, DNA per dish increased until day 14 and subsequently remained stable at approximately 100 micrograms/dish. The MBC also increased from days 0 to 7, and remained stable until day 14. On day 20, the MBC had declined by approximately 60% to 0.21 ng T3/mg DNA, at which time the neuron population was decreased. The extracted nuclear receptor from brain cell cultures had a sedimentation coefficient of 3.6S. The relative binding affinities of the nuclear receptor for T3 and several analogs were identical to those found in vivo, making significant contamination of the nuclei with cytosolic or serum binding proteins very unlikely. Nuclei isolated from long term, neuron-free glial cell cultures failed to show any consistent high affinity saturable T3 binding.(ABSTRACT TRUNCATED AT 400 WORDS)

Recurrent prolactinoma and meningioma following irradiation and bromocriptine treatment.

This case report describes a 45-year-old man with a massive extrasellar prolactinoma, treated initially with surgery and radiotherapy, who experienced a dramatic reduction of the bulk of his tumor but persistence and subsequent progression of an extrasellar portion while receiving long-term bromocriptine therapy, despite stable, suppressed prolactin levels. Although the residual tumor was thought to be adenomatous tissue unresponsive to bromocriptine, a meningioma was ultimately diagnosed. Because the meningioma may have been radiation-induced, clinicians are reminded to consider a second neoplasm in cases of apparent bromocriptine treatment failures, especially when prolactin levels are stable.

The regional hypothalamic distribution of type II 5'-monodeiodinase in euthyroid and hypothyroid rats.

The brain topographical distribution of type II 5'-monodeiodinase (5'D-II), which converts thyroxine (T4) to triiodothyronine (T3), was studied in euthyroid and hypothyroid rats. Low levels of 5'D-II activity were detected in the median eminence, but not in any other brain regions of euthyroid rats. The arcuate nucleus and median eminence were also the sites of highest 5'D-II activity in brains of hypothyroid rats. Under these conditions, the paraventricular nucleus contained almost no detectable 5'D-II, while intermediate enzyme activity was present in other medial basal hypothalamic sites.

Random generation and the executive control of working memory.

A series of experiments explores the capacity for generating sequences of random responses, relating it to the central executive component of working memory. Experiment 1 shows a broadly similar pattern of redundancy increasing with speed of generation for both the verbal generation of digits and the manual pressing of keys. In both cases deviations from randomness are shown to reflect the increasing use of a limited number of stereotyped response sets. The remaining experiments use keyboard generation. Experiment 2 demonstrates that concurrent immediate serial recall decreases randomness, and that longer recall sequences produce less random output. Experiments 3 and 4 show that whereas simple counting has no effect on randomness, serial recall, semantic category generation, and concurrent digit generation have substantial effects, and a concurrent fluid intelligence test has the greatest influence on the randomness of key pressing. It is suggested that the task of random generation resembles that of category fluency because it requires the subject to switch retrieval plans and inhibit repetition. On this basis it is predicted that a task involving repeated switching of categories will interfere with generation, despite being predictable and having a low memory load. Experiments 5 and 6 confirm this prediction. Strengths and limitations of the switching hypothesis are discussed, as are the implications of our results for the analysis of executive processes.

Hypervitaminosis D associated with drinking milk.

BACKGROUND: Vitamin D has been added to milk in the United States since the 1930s to prevent rickets. We report the unusual occurrence of eight cases of vitamin D intoxication that appear to have been caused by excessive vitamin D fortification of dairy milk. METHODS: Medical records were reviewed and a dietary questionnaire was sent to eight patients who had unexplained hypervitaminosis D. Vitamin D analyses with high-performance liquid chromatography were performed on samples of the patients' serum, the dairy milk they drank, and the vitamin D concentrate added to the milk. RESULTS: All eight patients drank milk produced by a local dairy in amounts ranging from 1/2 to 3 cups (118 to 710 ml) daily. All had elevated serum 25-hydroxyvitamin D concentrations (mean [+/- SD], 731 +/- 434 nmol per liter [293 +/- 174 ng per milliliter]). Six of the eight patients had elevated serum vitamin D3 concentrations. Of the eight patients, seven had hypercalcemia and one had hypercalciuria but normocalcemia (mean serum calcium, 3.14 +/- 0.51 mmol per liter [12.6 +/- 2.1 mg per deciliter]). Analysis of the dairy's vitamin D-fortified milk revealed concentrations of vitamin D3 (cholecalciferol) that ranged from undetectable to as high as 232,565 IU per quart (245,840 IU per liter). An analysis of the concentrate that was used to fortify the milk, labeled as containing vitamin D2 (ergocalciferol), revealed that it contained vitamin D3. CONCLUSIONS: Hypervitaminosis D may result from drinking milk that is incorrectly and excessively fortified with vitamin D. Milk that is fortified with vitamin D must be carefully monitored.