Discrimination of single features and conjunctions by children.

Stimuli that are discriminated by a conjunction of features can show more rapid early processing in adults. To determine how this facilitation effect develops, the processing of visual features and their conjunction was examined in 7-12-year-old children. The children completed a series of tasks in which they made a target-non-target judgement as a function of shape only, colour only or shape and colour features, while event-related potentials were recorded. To assess early stages of feature processing the posteriorly distributed P1 and N1 were analysed. Attentional effects were seen for both components. P1 had a shorter latency and P1 and N1 had larger amplitudes to targets than non-targets. Task effects were driven by the conjunction task. P1 amplitude was largest, while N1 amplitude was smallest for the conjunction targets. In contrast to larger left-sided N1 in adults, N1 had a symmetrical distribution in the children. N1 latency was shortest for the conjunction targets in the 9-10-year olds and 11-12-year olds, demonstrating facilitation in children, but which continued to develop over the pre-teen years. These data underline the sensitivity of early stages of processing to both top-down modulations and the parallel binding of non-spatial features in young children. Furthermore, facilitation effects, increased speed of processing when features need to be conjoined, mature in mid-childhood, arguing against a hierarchical model of visual processing, and supporting a rapid, integrated facilitative model.     

Spatiotemporal analysis of event-related potentials to upright, inverted, and contrast-reversed faces: effects on encoding and recognition

In an n-back face recognition task where subjects responded to repeated stimuli, ERPs were recorded to upright, inverted, and contrast-reversed faces. The effects of inversion and contrast reversal on face encoding and recognition were investigated using the multivariate spatiotemporal partial least squares (PLS) analysis. The configural manipulations affected early processing (100-200 ms) at posterior sites: Inversion effects were parietal and lateral, whereas contrast-reversal effects were more occipital and medial, suggesting different underlying generators. A later reactivation of face processing areas was unique to inverted faces, likely due to processing difficulties. PLS also indicated that the "old-new" repetition effect was maximal for upright faces and likely involved frontotemporal areas. Marked processing differences between inverted and contrast-reversed faces were seen, but these effects were similar at encoding and recognition.     

Correlations of serum concentrations of 1,25-dihydroxyvitamin D, phosphorus, and parathyroid hormone in tumoral calcinosis

The inherited metabolic disorder tumoral calcinosis is characterized by elevated serum phosphorus and 1,25-dihydroxyvitamin D [1,25-(OH)2D] levels and paraarticular calcific tumors. The pathogenesis of this disease is obscure, but an elevated renal phosphate reabsorption threshold and increased production of 1,25-(OH)2D are postulated as defects. We studied nine affected patients and found that both serum phosphorus and renal phosphate reabsorption threshold (TmP/GFR) were positively correlated with serum 1,25-(OH)2D levels. Since tumoral calcinosis is a disorder with abnormal renal phosphate transport, we compared the TmP/GFR and serum 1,25-(OH)2D levels to values obtained in patients with two other diseases with renal phosphate transport defects: oncogenic osteomalacia and X-linked hypophosphatemic rickets. We found a significant correlation between TmP/GFR and 1,25-(OH)2D levels in all three diseases, suggesting that in these diseases 1,25-(OH)2D production is regulated in some manner by phosphate transport. Furthermore, previous work indicated that in tumoral calcinosis broad variation exists in serum phosphorus levels. In our patients a negative correlation was found between the serum PTH concentrations and both serum phosphorus levels and TmP/GFR values, respectively. We postulate that although the basic defect in tumoral calcinosis most likely resides in the proximal renal tubular cell, the variation in serum phosphorus levels and possibly disease expression is modulated in part by PTH.     

Calcium supplementation lowers serum parathyroid hormone levels in elderly subjects

To determine the effect of calcium supplementation on parathyroid hormone levels (PTH) in a group of elderly subjects at risk for developing Type II (senile) osteoporosis, 40 healthy volunteers participated in a randomized double-blind crossover study. Calcium carbonate or placebo was administered for 4 weeks, followed by a 4-week administration of the alternative intervention. Fasting blood samples and 24-hour urine collections were obtained at baseline, and at the end of each intervention period. Calcium supplementation (1000 mg/day) decreased serum PTH levels from a mean of 50.1 +/- 3.0 pg/ml to 41.9 +/- 2.4 pg/ml (p less than .001). Additionally, urine calcium excretion significantly increased during calcium administration (from 3.64 mmol/mmol creatinine at baseline to 4.28 mmol/mmol creatinine), but creatinine clearances and serum calcium levels remained unchanged. Type II osteoporosis has been associated with age-related increases in PTH levels. We have demonstrated the ability of increased calcium intake to decrease these levels, which may have implications for the management of a subset of patients with involutional osteoporosis.     

A reliable MR measurement of medial temporal lobe width from the Sunnybrook Dementia Study

We studied the hippocampal angle and spatial relationships of medial temporal lobe (MTL) structures, using midbrain colliculi and inter-collicular sulcus (ICS) as landmarks, and measured MTL width on axial 3D-T1-weighted MRI at ICS level in 41 normal, aged participants. Mean hippocampal angle was 29 degrees (range 17-42 degrees ) caudal to the anterior-posterior commissure (AC-PC) line. The slice at the ICS, parallel to the long axis of the hippocampus, best revealed a longitudinal view of hippocampus and parahippocampal gyrus in 76% of participants, compared to only 7% when slices were 20 degrees caudal to orbitomeatal line (OML), an accepted technique used to examine MTL width in previous CT studies. The MTL width measured midway and at its thinnest between the anterior-posterior borders of the midbrain was highly reproducible (intraclass correlation coefficients >0.98) using these new methods. These simple decision rules, individualized orientation along the hippocampus and using a standardized landmark like the ICS, make these measures more comparable across subjects, and hence more useful in detecting and monitoring MTL atrophy in dementia.     

Three brain SPECT region-of-interest templates in elderly people: normative values, hemispheric asymmetries, and a comparison of single- and multihead cameras.

The purpose of this study was to generate anatomically guided region-of-interest (ROI) brain SPECT templates based on scans of elderly healthy volunteers. We describe normal tracer uptake and hemispheric asymmetries for each of 3 camera systems and compare these characteristics among systems. METHODS: 99mTc-hexamethyl propyleneamine oxime SPECT scans were acquired from 28 elderly healthy volunteers (mean age [+/-SD], 70.3 +/- 6.5 y) on a single-head rotating gamma camera (n = 15) or on dual- (n = 18) or triple-head (n = 13) cameras. The average number of counts in each ROI was calculated and referenced to counts in a cerebellar ROI, providing semiquantitative regional cerebral blood flow (rCBF) ratios. For the templates and ROI map, base images of a healthy volunteer were obtained with each camera. Data from individuals scanned with 2 cameras on the same day (n = 15) were used to evaluate rCBF differences across cameras. For each camera, averaged SPECT templates were made using automated image registration. The base volunteer's T1-weighted MR image was converted to stereotactic space with dimensions similar to those of the SPECT templates, and 79 bilateral ROIs were defined. To obtain ROI rCBF ratios, we aligned individual images to their appropriate template and then to this modified MR image. RESULTS: The ROI coefficients of variation indicated that the fit of the ROIs was acceptable (0.07-0.35). Mean rCBF ratios ranged from 0.57 to 1.0, 0.67 to 1.01, and 0.63 to 1.00 for single-, dual-, and triple-head cameras, respectively. The cuneus, occipital cortex, occipital pole, middle temporal gyrus, and posterior middle frontal gyrus showed consistent hemispheric asymmetry (right side greater than left side in 83%-100% of individuals). Mean rCBF ratios did not differ between dual- and triple-head cameras, whereas the ratios for single- and dual-head cameras differed significantly (39 ROIs differed), even after smoothing and filtering the dual-head images to the level of the single-head images. CONCLUSION: The use of SPECT templates based on elderly healthy volunteers is an important feature of this technique because most available templates have used young individuals. Another important feature is the use of MR image-based ROIs. These procedures are versatile because they use more than 1 camera. They can easily be implemented in clinical and research settings to detect camera-specific, abnormal deviations in rCBF ROI ratios and asymmetry magnitudes in diseases associated with aging, such as stroke and dementia.     

Calcitonin stimulation of renal 25-hydroxyvitamin D-1 alpha-hydroxylase activity in hypophosphatemic mice. Evidence that the regulation of calcitriol production is not universally abnormal in X-linked hypophosphatemia.

Hypophosphatemia (Hyp) mice have defective regulation of 25(OH)D-1 alpha-hydroxylase activity in response to hypophosphatemia, hypocalcemia, and parathyroid hormone (PTH) administration. However, recent observations support the existence of anatomically distinct, independently regulated renal 1 alpha-hydroxylase systems in mammalian proximal convoluted and straight tubules. To more completely define the extent of the 1 alpha-hydroxylase regulatory defect in Hyp-mice, we compared enzyme maximum velocity in normal and mutants after infusion of calcitonin. Upon stimulation, renal 1 alpha-hydroxylase activity increased to similar levels in normal and Hyp-mouse renal homogenates. Moreover, time-course and dose-dependence studies revealed similar patterns of response in the animal models. Subsequently, we examined whether PTH and calcitonin stimulatory effects on enzyme activity are mediated through different mechanisms. In both animal models administration of PTH and calcitonin increased enzyme activity to levels greater than those obtained after maximal stimulation by either hormone alone, consistent with additive effects. These observations indicate that a calcitonin-sensitive component of 1 alpha-hydroxylase is not compromised in the X-linked hypophosphatemic syndrome.     

The ZNF804A Gene: Characterization of a Novel Neural Risk Mechanism for the Major Psychoses

Schizophrenia and bipolar disorder share genetic risk, brain vulnerability, and clinical symptoms. The ZNF804A risk variant, rs1344706, confers susceptibility for both disorders. This study aimed to identify neural mechanisms common to both schizophrenia and bipolar disorder through this variant''s potential effects on cortical thickness, white matter tract integrity, and cognitive function. Imaging, genetics, and cognitive measures were ascertained in 62 healthy adults aged between 18 and 59 years. High-resolution multimodal MRI/DTI imaging was used to measure cortical thickness and major frontotemporal and interhemispheric white matter tracts. The general linear model was used to examine the influence of the ZNF804A rs1344706 risk variant on cortical thickness, white matter tract integrity, and cognitive measures. Individuals homozygous for the risk variant (‘A'' allele) demonstrated reduced cortical gray matter thickness in the superior temporal gyrus, and in the anterior and posterior cingulate cortices compared with C-allele carriers. No effect of the risk variant on microstructural integrity of white matter tracts was found. Reduced attention control was found in risk allele homozygotes, aligning with findings in the anterior cingulate cortex. Our data provide a novel, genetically based neural risk mechanism for the major psychoses by effects of the ZNF804A risk variant on neural structures and cognitive function susceptible in both disorders. Our findings link genetic, imaging, and cognitive susceptibility relevant to both schizophrenia and bipolar disorder.     

Primary hyperparathyroidism: a new experimental animal model

Although potentially useful in the understanding of hypercalcemic states, a satisfactory animal model of primary hyperparathyroidism has not been developed. Models that use transplants of supernumerary parathyroid (PT) glands or chronic parathyroid hormone (PTH) infusion are not ideal for many reasons. We report a new animal model in which athymic nude mice were used as recipients of human PT tissue heterografts. Three groups received 14, six, or one piece of PT adenoma tissue, and one group received six pieces of normal PT tissue. The significantly higher PTH levels in mice that received adenoma heterografts versus those with similar amounts of normal tissue suggest that adenomatous tissue is functionally distinct. A dose-response relationship between induction of hypercalcemia and the number of pieces implanted was in evidence, although only a small percentage of the mice with high PTH levels developed hypercalcemia. This differential response could be the result of any of several factors: (1) loss of ability to secrete bioactive PTH, (2) differing secretion rates among donor adenomas, (3) variability in host responsiveness to human PTH, and (4) requirement of additional factor(s) to generate consistently the hypercalcemia characteristic of human primary hyperparathyroidism.