Sex differentiation of brain structures in autism: Findings from a gray matter asymmetry study.

Autism spectrum disorder (ASD) is diagnosed much more often in males than females. This male predominance has prompted a number of studies to examine how sex differences are related to the neural expression of ASD. Different theories, such as the "extreme male brain" theory, the "female protective effect" (FPE) theory, and the gender incoherence (GI) theory, provide different explanations for the mixed findings of sex-related neural expression of ASD. This study sought to clarify whether either theory applies to the brain structure in individuals with ASD by analyzing a selective high-quality data subset from an open data resource (Autism Brain Imaging Data Exchange I and II) including 35 males/35 females with ASD and 86 male/86 female typical-controls (TCs). We examined the sex-related changes in ASD in gray matter asymmetry measures (i.e., asymmetry index, AI) derived from voxel-based morphometry using a 2 (diagnosis: ASD vs. TC) × 2 (sex: female vs. male) factorial design. A diagnosis-by-sex interaction effect was identified in the planum temporale/Heschl's gyrus: (i) compared to females, males exhibited decreased AI (indicating more leftward brain asymmetry) in the TC group, whereas AI was greater (indicating less leftward brain asymmetry) for males than for females in the ASD group; and (ii) females with ASD showed reduced AI (indicating more leftward brain asymmetry) compared to female TCs, whereas there were no differences between ASDs and TCs in the male group. This interaction pattern supports the FPE theory in showing greater brain structure changes (masculinization) in females with ASD. LAY SUMMARY: To understand the neural mechanisms underlying male predominance in autism spectrum disorder (ASD), we investigated the sex differences in ASD-related alterations in brain asymmetry. We found greater changes in females with ASD compared with males with ASD, revealing a female protective effect. These findings provide novel insights into the neurobiology of sex differences in ASD.

Training-induced brain activation and functional connectivity differentiate multi-talker and single-talker speech training.

In second language acquisition studies, the high talker variability training approach has been frequently used to train participants to learn new speech patterns. However, the neuroplasticity induced by training is poorly understood. In the present study, native English speakers were trained on non-native pitch patterns (linguistic tones from Mandarin Chinese) in multi-talker (N = 16) or single-talker (N = 16) training conditions. We focused on two aspects of multi-talker training, voice processing and lexical phonology accessing, and used functional magnetic resonance imaging (fMRI) to measure the brain activation and functional connectivity (FC) of two regions of interest in a tone identification task conducted before and after training, namely the anterior part of the right superior temporal gyrus (aRSTG) and the posterior left superior temporal gyrus (pLSTG). The results showed distinct patterns of associations between neural signals and learning success for multi-talker training. Specifically, post-training brain activation in the aRSTG and FC strength between the aRSTG and pLSTG were correlated with learning success in the multi-talker training group but not in the single-talker group. These results suggest that talker variability in the training procedure may enhance neural efficiency in these brain areas and strengthen the cooperation between them. Our findings highlight the brain processing of newly learned speech patterns is influenced by the given training approach.

Resting-state low-frequency fluctuations reflect individual differences in spoken language learning.

A major challenge in language learning studies is to identify objective, pre-training predictors of success. Variation in the low-frequency fluctuations (LFFs) of spontaneous brain activity measured by resting-state functional magnetic resonance imaging (RS-fMRI) has been found to reflect individual differences in cognitive measures. In the present study, we aimed to investigate the extent to which initial spontaneous brain activity is related to individual differences in spoken language learning. We acquired RS-fMRI data and subsequently trained participants on a sound-to-word learning paradigm in which they learned to use foreign pitch patterns (from Mandarin Chinese) to signal word meaning. We performed amplitude of spontaneous low-frequency fluctuation (ALFF) analysis, graph theory-based analysis, and independent component analysis (ICA) to identify functional components of the LFFs in the resting-state. First, we examined the ALFF as a regional measure and showed that regional ALFFs in the left superior temporal gyrus were positively correlated with learning performance, whereas ALFFs in the default mode network (DMN) regions were negatively correlated with learning performance. Furthermore, the graph theory-based analysis indicated that the degree and local efficiency of the left superior temporal gyrus were positively correlated with learning performance. Finally, the default mode network and several task-positive resting-state networks (RSNs) were identified via the ICA. The "competition" (i.e., negative correlation) between the DMN and the dorsal attention network was negatively correlated with learning performance. Our results demonstrate that a) spontaneous brain activity can predict future language learning outcome without prior hypotheses (e.g., selection of regions of interest--ROIs) and b) both regional dynamics and network-level interactions in the resting brain can account for individual differences in future spoken language learning success.

Pitch Processing in Tonal-Language-Speaking Children with Autism: An Event-Related Potential Study.

The present study investigated pitch processing in Mandarin-speaking children with autism using event-related potential measures. Two experiments were designed to test how acoustic, phonetic and semantic properties of the stimuli contributed to the neural responses for pitch change detection and involuntary attentional orienting. In comparison with age-matched (6-12 years) typically developing controls (16 participants in Experiment 1, 18 in Experiment 2), children with autism (18 participants in Experiment 1, 16 in Experiment 2) showed enhanced neural discriminatory sensitivity in the nonspeech conditions but not for speech stimuli. The results indicate domain specificity of enhanced pitch processing in autism, which may interfere with lexical tone acquisition and language development for children who speak a tonal language.

Feedback-related negativity encodes outcome uncertainty in the gain domain but not in the loss domain.

Outcome uncertainty plays an important role in decision making. The present study used event-related potentials (ERP) combined with a simple gambling task to investigate the time course of outcome uncertainty processing in the gain and the loss domains. Behaviorally, participants showed a preference for the uncertain option in the gain domain, whereas they showed no such preference in the loss domain. In ERP analyses, the feedback-related negativity (FRN) amplitudes mirrored the behavioral results: for gains, cue-elicited FRN amplitudes were more negative for uncertain than for certain cues, whereas for losses, cue-elicited FRN amplitudes for certain cues and uncertain cues were not different. In contrast, the P300 amplitude was sensitive to the valence of cues (gains or losses) but not to the uncertainty of the outcome. These results suggest that the outcome uncertainty is rapidly and differentially processed in the gain and loss domains.

[Effect of blood glucose control after small intestine exclusion surgery in Goto-Kakizaki rat with type 2 diabetes mellitus].

OBJECTIVE: To evaluate the effect of diabetic control after small intestine exclusion surgery in Goto-Kakizaki (GK) rat with type 2 diabetes mellitus. METHODS: GK type 2 diabetic rats underwent duodenal bypass (Group A, n = 8) creating a shortcut for ingested nutrients with bypassing duodenum alone, or duodenal-jejunal bypass (Group B, n = 8), a stomach-preserving RYGB excluding duodenum and proximal jejunum, or duodenum and total jejunum exclusion (Group C, n = 8), or sub-total small intestine exclusion (Group D, n = 8) creating a shortcut for ingested nutrients with bypassing duodenum, jejunum and sub-total ileum. Controls were pair-fed (PF) sham-operated and untreated GK rats (Group SO, n = 8). Rats were observed for 24 weeks after surgery. Fasting blood glucose (FBG) level was determined on a Surestep plus blood glucose meter (Lifescan) at 0, 1, 3, 6, 12, 24 week. Hemoglobin A1c (HbA1c) level was measured at 0, 12, 24 week on VARIANT Hemoglobin A1c Program (Bio-Ray) with high performance liquid chromatography (HPLC) method. RESULTS: The fasting blood glucose and HbA1c levels significantly decreased after surgery in all the operative groups through the entire follow-up period [Group B (FBG before surgery and 1 week after: (162 +/- 44) mg/dl vs (80 +/- 19) mg/dl; HbAlc before surgery and 12 week after: (8.2 +/- 2.2)% vs (5.1 +/- 1.5)%, P < 0.05 or P < 0.01]; while FBG had no differences before 12 week and significantly increased at 12 week (164 +/- 44) mg/dl and 24 week (180 +/- 42) mg/dl in group SO [preoperative (145 +/- 35) mg/dl, P < 0.01]. As compared with sham-operated rats, all the operative groups showed reduced blood-glucose and HbA1c levels through the entire follow-up period (P < 0.05 or P < 0.01). The FBG and HbA1c levels in Group B significantly decreased versus Group A [24 week (FBG: (82 +/- 21) mg/dl vs (111 +/- 27) mg/dl; HbA1c: (3.9 +/- 0.9)% vs (5.4 +/- 1.2)%, P < 0.05], indicating that duodenal-jejunal bypass had markedly a better effect of diabetic control. But Groups B, C and D were similar to one another (P > 0.05), suggesting that a potential role of proximal gut in the pathogenesis of disease. CONCLUSION: In spontaneous type 2 diabetes mellitus rats, all the small intestinal exclusion including proximal gut are effective in glucose control. In terms of intestinal nutrient absorption, duodenal-jejunal bypass may be an ideal surgery for clinical diabetic control. These findings suggest a potential role of proximal intestine in pathogenesis of type 2 diabetes mellitus.

[Effect of diabetes control after small intestine exclusion surgery in Goto-Kakizaki rat with non-obese type 2 diabetes mellitus].

OBJECTIVE: To evaluate the effect and possible mechanisms of diabetes control after small intestine exclusion surgery in Goto-Kakizaki (GK) rat with non-obese type 2 diabetes mellitus. METHODS: Forty GK rats with non-obese type 2 diabetes mellitus underwent duodenal bypass (Group A, n = 8), which creates a shortcut for ingested nutrients bypassing duodenum alone; duodenal-jejunal bypass (Group B, n = 8), a stomach-preserving RYGB that excludes the duodenum and proximal jejunum; duodenum and total jejunum exclusion (Group C, n = 8); sub-total small intestine exclusion (Group D, n = 8), which creates a shortcut for ingested nutrients bypassing duodenum, jejunum and sub-total ileum; controls were pair-fed (PF) sham-operated and untreated GK rats (Group SO, n = 8). The rats were observed for 24 weeks after surgery. Body weight, food intake and fasting blood glucose level were tested at 0, 1, 3, 6, 12, 24 weeks after the operation in those groups. The concentrations of insulin and glucagon-like peptide-1 (GLP-1) concentrations were measured before (baseline) and then 30, 60, 120, and 180 minutes after OGTT at 0, 12, 24 weeks after the operation. RESULTS: Mean operating time of all groups was similar. The mean body weight and food intake decreased significantly at 1 week after surgery (P < 0.01) and with no differences among the groups. Fasting blood glucose level decreased significantly after surgery in all the operation groups through the entire follow-up period (P < 0.05). No significant changes in fasting blood glucose level in SO group was found in 12 weeks after the operation, and it increased at 12 and 24 weeks after. Fasting blood glucose levels in group B decreased significantly compared with group A (P < 0.05), but no difference was found among group B, C and D (P > 0.05). Oral glucose-stimulated peak (30 min) levels of blood insulin and GLP-1 increased markedly in operation groups (A, B, C and D) after surgery (P < 0.01). Compared with group A, peak levels of blood insulin and GLP-1 in group B were strikingly higher (P < 0.05), but no difference was found when compared with group C or D (P > 0.05). CONCLUSIONS: In spontaneously non-obese type 2 diabetes mellitus rats, small intestinal exclusion including proximal gut is effective in terms of glucose control and has no direct relation with body weight and food intake loss. Restoration of the first-phase insulin secretion and high secretion of GLP-1 in type 2 diabetic subjects after gastrointestinal bypass surgery seem to be helpful to diabetes control. Taking intestinal nutrient absorption into consideration, duodenal-jejunal bypass may be a better surgery for diabetes control.