Atypical MEG inter-subject correlation during listening to continuous natural speech in dyslexia.

Listening to speech elicits brain activity time-locked to the speech sounds. This so-called neural entrainment to speech was found to be atypical in dyslexia, a reading impairment associated with neural speech processing deficits. We hypothesized that the brain responses of dyslexic vs. normal readers to real-life speech would be different, and thus the strength of inter-subject correlation (ISC) would differ from that of typical readers and be reflected in reading-related measures. We recorded magnetoencephalograms (MEG) of 23 dyslexic and 21 typically-reading adults during listening to ~10 â€‹min of natural Finnish speech consisting of excerpts from radio news, a podcast, a self-recorded audiobook chapter and small talk. The amplitude envelopes of band-pass-filtered MEG source signals were correlated between subjects in a cortically-constrained source space in six frequency bands. The resulting ISCs of dyslexic and typical readers were compared with a permutation-based t-test. Neuropsychological measures of phonological processing, technical reading, and working memory were correlated with the ISCs utilizing the Mantel test. During listening to speech, ISCs were mainly reduced in dyslexic compared to typical readers in delta (0.5-4 â€‹Hz) and high gamma (55-90 â€‹Hz) frequency bands. In the theta (4-8 â€‹Hz), beta (12-25 â€‹Hz), and low gamma (25-45 â€‹Hz) bands, dyslexics had enhanced ISCs to speech compared to controls. Furthermore, we found that ISCs across both groups were associated with phonological processing, technical reading, and working memory. The atypical ISCs to natural speech in dyslexics supports the temporal sampling deficit theory of dyslexia. It also suggests over-synchronization to phoneme-rate information in speech, which could indicate more effort-demanding sampling of phonemes from speech in dyslexia. These irregularities in parsing speech are likely some of the complex neural factors contributing to dyslexia. The associations between neural coupling and reading-related skills further support this notion.

Infancy and early childhood maturation of neural auditory change detection and its associations to familial dyslexia risk.

OBJECTIVE: We investigated early maturation of the infant mismatch response MMR, including mismatch negativity (MMN), positive MMR (P-MMR), and late discriminative negativity (LDN), indexing auditory discrimination abilities, and the influence of familial developmental dyslexia risk. METHODS: We recorded MMRs to vowel, duration, and frequency deviants in pseudo-words at 0, 6, and 28 months and compared MMRs in subgroups with vs. without dyslexia risk, in a sample over-represented by risk infants. RESULTS: Neonatal MMN to the duration deviant became larger and earlier by 28 months; MMN was elicited by more deviants only at 28 months. The P-MMR was predominant in infancy; its amplitude increased by 6 and decreased by 28 months; latency decreased with increasing age. An LDN emerged by 6 months and became larger and later by 28 months. Dyslexia risk affected MMRs and their maturation. CONCLUSIONS: MMRs demonstrate an expected maturational pattern with 2-3 peaks by 28 months. The effects of dyslexia risk are prominent but not always as expected. SIGNIFICANCE: This large-scale longitudinal study shows MMR maturation with three age groups and three deviants. Results illuminate MMR's relation to the adult responses, and hence their cognitive underpinnings, and help in identifying typical/atypical auditory development in early childhood.

Neuromagnetic speech discrimination responses are associated with reading-related skills in dyslexic and typical readers.

Poor neural speech discrimination has been connected to dyslexia, and may represent phonological processing deficits that are hypothesized to be the main cause for reading impairments. Thus far, neural speech discrimination impairments have rarely been investigated in adult dyslexics, and even less by examining sources of neuromagnetic responses. We compared neuromagnetic speech discrimination in dyslexic and typical readers with mismatch fields (MMF) and determined the associations between MMFs and reading-related skills. We expected weak and atypically lateralized MMFs in dyslexic readers, and positive associations between reading-related skills and MMF strength. MMFs were recorded to a repeating pseudoword /ta-ta/ with occasional changes in vowel identity, duration, or syllable frequency from 43 adults, 21 with confirmed dyslexia. Phonetic (vowel and duration) changes elicited left-lateralized MMFs in the auditory cortices. Contrary to our hypothesis, MMF source strengths or lateralization did not differ between groups. However, better verbal working memory was associated with stronger left-hemispheric MMFs to duration changes across groups, and better reading was associated with stronger right-hemispheric late MMFs across speech-sound changes in dyslexic readers. This suggests a link between neural speech processing and reading-related skills, in line with previous work. Furthermore, our findings suggest a right-hemispheric compensatory mechanism for language processing in dyslexia. The results obtained promote the use of MMFs in investigating reading-related brain processes.

Exendin-4 improves the oral glucose tolerance in diabetic rats: pancreas regeneration, better function of pancreatic islets, or impaired glucose uptake?

One major obstacle for successful clinical transplantation of isolated pancreatic islets (PI) is their limited survival in vivo. The aim of this study was to analyze the functional and morphological regeneration of PI in diabetic rats by Exendin-4 (Ex4) treatment in vivo. Male Wistar rats (n = 3/group) received 20 nmol/kg Ex4 i.p. for 20 days (day 0 to day +20). Diabetes was induced with 50 mg/kg streptozotocin i.v. on day -3 or on day +5. Diabetic and normal control rats received 0.9% NaCl i.p. instead. Body weight (BW), daily blood glucose (BG) and levels, oral glucose tolerance (OGT) were tested on day -5, day +10, day +20, and on day +22, ie, 48 hours after the last Ex4 injection. Histology of the pancreata ended the study on day +24. In vivo application of Ex4 could not prevent the development of diabetes. Injection of Ex4 led to a significant decrease in postprandial BG levels to 35% for 12 hours. Surprisingly, Ex4 increased postprandial BG levels up to 20% in normal rats. Ex4-treated rats showed better OGT than untreated controls. Interestingly, 48 hours after the last Ex4 injection on day +22 OGT was completely impaired. The Ex4-treated rats lost BW much faster than the untreated controls, and showed signs of gastroparesis at autopsy. Immunohistochemistry of the pancreata documented no signs of islet regeneration. Improvement of OGT in diabetic rats after Ex4 treatment may be explained by increased insulin release from the individual PI, which was confirmed by perifusion studies with isolated PI in vitro (data not shown). Yet, Ex4 may also exert an influence on the gastrointestinal tract as it delays the uptake of glucose during gastroparesis.

Use of the continuous glucose monitoring system in Goettingen Minipigs, with a special focus on the evaluation of insulin-dependent diabetes.

OBJECTIVES: Adult pig islet isolation has greatly improved in the past few years. Islet grafts may now be tested in large animals. Continuous Glucose Monitoring System (CGMS) was applied to diabetic Goettingen Minipigs (GMP) to improve the management of hyperglycemia and hypoglycemia and their welfare before transplantation. METHODS: GMP (25-35 kg) received a minipig diet once daily. Diabetes was induced by streptozotocin (STZ; 150 mg/kg intravenous [IV]; n = 5) or by surgical pancreatectomy (PGMP; n = 3). Interstitial glucose concentration (IGC) was monitored continuously with an implanted sensor; CGMS was calibrated using conventional blood glucose tests 3-4 times per day; CGMS data were fed into the monitor memory and analyzed using CGMS software. RESULTS: Glucose sensors were handled accurately. Diabetes occurred 2-3 days after STZ or immediately after pancreatectomy with basal C-peptide secretion of <0.4 ng/mL (measured using intravenous glucose tolerance test) and prompt loss of body weight. Insulin substitution was necessary to keep the GMP in good condition for up to 5-6 months, with stable body weight and normal behavior. Some GMP became hypoglycemic, which was only documented by CGMS, but not by conventional glucose assays. Tight glucose control and substitution of exocrine enzymes (Creon 25,000 E/d) reduced morbidity of the PGMP, which was then comparable with that of STZ-GMP. CONCLUSIONS: The CGMS, developed for humans, is equally suitable for the 2 GMP diabetes models. Close-meshed glucose monitoring and insulin treatment improved the general condition of the diabetic GMP, ie, the islet graft recipients, and will thus greatly add to posttransplantation success.