Children at risk for dyslexia show deficient left-hemispheric memory representations for new spoken word forms.

Developmental dyslexia is a specific learning disorder with impairments in reading and spelling acquisition. Apart from literacy problems, dyslexics show inefficient speech encoding and deficient novel word learning, with underlying problems in phonological processing and learning. These problems have been suggested to be related to deficient specialization of the left hemisphere for language processing. To examine this possibility, we tracked with magnetoencephalography (MEG) the activation of the bilateral temporal cortices during formation of neural memory traces for new spoken word forms in 7-8-year-old children with high familial dyslexia risk and in controls. The at-risk children improved equally to their peers in overt repetition of recurring new word forms, but were poorer in explicit recognition of the recurring word forms. Both groups showed reduced activation for the recurring word forms 400-1200 ms after word onset in the right auditory cortex, replicating the results of our previous study on typically developing children (Nora et al., 2017, Children show right-lateralized effects of spoken word-form learning. PLoS ONE 12(2): e0171034). However, only the control group consistently showed a similar reduction of activation for recurring word forms in the left temporal areas. The results highlight the importance of left-hemispheric phonological processing for efficient phonological representations and its disruption in dyslexia.

Dynamic Time-Locking Mechanism in the Cortical Representation of Spoken Words.

Human speech has a unique capacity to carry and communicate rich meanings. However, it is not known how the highly dynamic and variable perceptual signal is mapped to existing linguistic and semantic representations. In this novel approach, we used the natural acoustic variability of sounds and mapped them to magnetoencephalography (MEG) data using physiologically-inspired machine-learning models. We aimed at determining how well the models, differing in their representation of temporal information, serve to decode and reconstruct spoken words from MEG recordings in 16 healthy volunteers. We discovered that dynamic time-locking of the cortical activation to the unfolding speech input is crucial for the encoding of the acoustic-phonetic features of speech. In contrast, time-locking was not highlighted in cortical processing of non-speech environmental sounds that conveyed the same meanings as the spoken words, including human-made sounds with temporal modulation content similar to speech. The amplitude envelope of the spoken words was particularly well reconstructed based on cortical evoked responses. Our results indicate that speech is encoded cortically with especially high temporal fidelity. This speech tracking by evoked responses may partly reflect the same underlying neural mechanism as the frequently reported entrainment of the cortical oscillations to the amplitude envelope of speech. Furthermore, the phoneme content was reflected in cortical evoked responses simultaneously with the spectrotemporal features, pointing to an instantaneous transformation of the unfolding acoustic features into linguistic representations during speech processing.

Gastric carcinoid associated with the syndrome of hypergastrinemic atrophic gastritis. A prospective analysis of 11 cases.

The prevalence of gastric carcinoid in fundic atrophic gastritis is probably greater than previously recognized. To help elucidate the clinicopathology of this syndrome, we report a series of 11 patients with solitary or multicentric carcinoid tumors. In these patients, basal gastrin levels and density of fundic mucosal endocrine cells were greater than that for patients with uncomplicated fundic atrophic gastritis (p = 0.02 and p = 0.002, respectively). The polypoid tumors, of which the largest measured 30 mm, frequently showed characteristic endoscopic features. They were all situated in the fundic mucosa, which showed micronodular endocrine cell hyperplasia. Small, endoscopically evident tumorlets, or "early carcinoids," limited to the lamina propria were observed in some patients. These lesions may represent intermediate stages between micronodules and invasive carcinoids, all of which infiltrated at least into the muscularis mucosae of the gastric wall. Although some consistent characteristics features were noted, there were structural variations. The cells were argyrophil but nonargentaffin and did not stain with conventional mucus stains. They did not stain significantly for carcinoembryonic antigen (CEA). The secretory product of these tumors remains to be identified. Ultrastructurally, some tumors were mainly composed of enterochromaffinlike (ECL) cells, but in other tumors most of the cells could not be classified.

Gastric endocrine cell hyperplasia and carcinoid tumors in pernicious anemia.

Endoscopic screening in 123 patients with pernicious anemia (PA) yielded 4 patients with solitary and 1 patient with multiple gastric carcinoid tumors. Quantitative histologic studies of multiple standardized biopsy specimens showed a significantly increased number of fundic mucosal argyrophil endocrine cells in 40 patients with PA when compared with 15 patients with simple fundic atrophic gastritis (p = 0.002) or 8 normal controls (p = 0.0001). Patients with simple atrophic gastritis had increased numbers of fundic mucosal argyrophil cells as compared with normal controls (p = 0.02). A significant difference was also noticed in the number of antral mucosal argyrophil cells between patients with PA and normal controls (p = 0.01), but not between patients with PA and patients with simple atrophic gastritis. It is concluded that, in addition to having hyperplasia of gastric mucosal argyrophil endocrine cells, patients with PA run an increased risk of developing gastric argyrophil cell carcinoid tumors, which should be regarded as potentially malignant.

Left minineglect in dyslexic adults.

We searched for a core mechanism underlying the diverse behavioural and sensorimotor deficits in dyslexic subjects. In psychophysical temporal order judgement and line motion illusion tasks, adult dyslexics processed stimuli in the left visual hemifield significantly (approximately 15 ms) more slowly than normal readers, indicating a left-sided 'minineglect'. Furthermore, abrupt stimuli captured attention in both visual hemifields less effectively in dyslexics than in normal readers. These abnormalities could reflect right parietal lobe hypofunction, a consequence of a general magnocellular deficit demonstrated previously. Based on these and previous data, we propose a causal chain which could result in several sensory and cognitive deficits observed in dyslexic subjects.

Endocrine cell proliferation and carcinoid development: a review of new aspects of hypergastrinaemic atrophic gastritis.

The accumulating evidence of an association between antrum-sparing hypergastrinaemic atrophic gastritis, frequently associated with pernicious anaemia, and the occurrence of gastric carcinoid tumours is briefly reviewed. The development of argyrophil cell carcinoid tumours in the atrophic fundic mucosa seems to be related to argyrophil cell hyperplasia caused by hypergastrinaemia. Epidemiologic considerations indicate that the gastric carcinoid generally is underdiagnosed and that the incidence of this tumour is higher than previously recognized. The clinical relevance of minute gastric carcinoids, or endocrine cell 'adenomas', is obscure. However, larger tumours should be regarded as potentially malignant. These findings are relevant to the aspect of long-term medically induced achlorhydria leading to hypergastrinaemia.

Evaluation of gastric carcinoembryonic antigen analysis as an aid during screening for gastric neoplasia in atrophic gastritis.

The value of gastric juice and tissue carcinoembryonic antigen (CEA) analysis as an adjunct to endoscopic screening for gastric neoplasia was investigated in 61 patients with atrophic gastritis of whom 41 had other (superimposed) gastric lesions: six adenocarcinoma, four carcinoid, 23 regenerative polyps with or without dysplasia and eight fundic, or antral mucosal dysplasia. The gastric concentration of CEA did not differ between patient groups with different superimposed lesions. In these patients the gastric juice CEA concentrations were significantly increased in comparison with those in patients without superimposed lesions (p = 0.002). Gastric juice CEA concentrations above the upper range (+2SD) of those observed in normal controls were found in 40 (98%) of 41 patients with superimposed lesions and in 13 (65%) of 20 patients without such lesions (p = 0.001). At re-examination of 26 patients without neoplasia initially, after a mean interval of 32 months two (without polyps initially), had developed regenerative polyps, one an adenoma, and one an adenocarcinoma. These four had raised gastric juice CEA concentrations at the initial examination.

Relations between circulating gastrin and endocrine cell proliferation in the atrophic gastric fundic mucosa.

It has been suggested that gastrin may be a causative factor in the proliferation of gastric fundic mucosal endocrine cells, as seen in the Zollinger-Ellison syndrome and in atrophic gastritis with hypergastrinemia of antral origin. In the present study, morphometrically determined densities of endocrine cells in fundic mucosal biopsy specimens were related to basal levels of serum gastrin in 10 normal controls and 60 patients with achlorhydric fundic atrophic gastritis, of which 45 had pernicious anemia (5 with fundic mucosal carcinoid) and 15 had atrophic gastritis without pernicious anemia. The densities of fundic mucosal endocrine cells were positively related to the levels of serum gastrin (atrophic gastritis, rs = 0.65; atrophic gastritis and normal controls, rs = 0.72). The highest levels of serum gastrin were found in patients with carcinoid tumors (mean, 1659.3 pmol/l), followed by those in patients with focal hyperplasias (cluster formation) of endocrine cells (mean, 503.2 pmol/l) and those in patients without focal hyperplasias (mean, 304.4 pmol/l) (p = 0.03 and p = 0.04, respectively).