RESUMO
Children with autism spectrum disorder (ASD) show marked difficulties in reading comprehension, a complex cognitive skill fundamental to successful daily functioning that is associated with core executive functions. However, the neurophysiological mechanisms underlying reading comprehension deficits in these children remain elusive. Twenty-one right-handed males with high-functioning ASD (mean age = 10.24 years) and 23 age-, IQ-, educational level-, sex- and handedness-matched typically developing (TD; mean age = 10.14 years) individuals underwent a reading comprehension test and the semantic verbal fluency test that tapped core executive functions underlying reading comprehension during concurrent prefrontal functional near-infrared spectroscopy (fNIRS) measurement. Participants' information processing efficiency was also assessed. High-functioning ASD children exhibited general reading comprehension [main effect of group: F (1,40) = 7.58, p = 0.009], selective verbal fluency deficits [Group × category interaction: F (1,42) = 4.90, p = 0.032] and slower processing speed (t 42 = 2.36, p = 0.023). Regarding the hemodynamics of the prefrontal cortex (PFC), although ASD individuals showed comparable patterns of PFC brain activation to their healthy counterparts, lower PFC intrahemispheric [main effect of group: F (1,42) = 11.36, p = 0.002] and interhemispheric [main effect of group: F (1,42) = 7.79, p = 0.008] functional connectivity were evident during the semantic verbal fluency test. At the whole-group level, poorer reading comprehension performance was associated with poorer performance in the semantic verbal fluency test (r 42 = 0.508, p < 0.001). Moreover, poorer semantic verbal fluency test performance was associated with slower information processing speed (r 42 = -0.312, p = 0.044), which is associated with reduced left medial PFC functional connectivity (r 42 = -0.319, p = 0.040). Abnormal intrahemispheric and interhemispheric prefrontal hypoconnectivity is associated with deficits in executive processes essential for reading comprehension in ASD. Our study has provided important implications for the neuropsychological and neurophysiological mechanisms underlying reading comprehension deficits in ASD.
RESUMO
Individuals with autism spectrum disorder (ASD) are characterized by impairments in flexibly acquiring and maintaining new information, as well as in applying learned information for problem solving. However, the neural mechanism underpinning such impairments remains unclear. This study investigated the flexibility in the acquisition and application of visual information in ASD (aged 14−21) when they performed the Wisconsin Card Sorting Test (WCST). Behavioral data including response accuracy and latency, and prefrontal hemodynamic data measured by functional near-infrared spectroscopy (fNIRS), were collected when individuals performed WCST. Canonical general linear model and functional connectivity analyses were performed to examine the prefrontal activation and synchronization patterns, respectively. Results showed that although ASD individuals (n = 29) achieved comparable accuracy rates when compared with age- and intelligence quotient (IQ)-matched typically developing (TD; n = 26) individuals (F1,53 = 3.15, p = 0.082), ASD individuals needed significantly more time to acquire and apply WCST card sorting rules (F1,53 = 17.92, p < 0.001). Moreover, ASD individuals showed significantly lower prefrontal functional connectivity than TD individuals during WCST (F1,42 = 9.99, p = 0.003). The hypoconnectivity in ASD individuals was highly significant in the right lateral PFC in the acquisition condition (p = 0.005) and in the bilateral lateral PFC in the application condition (ps = 0.006). Furthermore, slower WCST reaction time was correlated with lower bilateral lateral PFC functional connectivity only in the application condition (ps = 0.003) but not the acquisition condition. Impairment in information acquisition and application is evident in ASD individuals and is mediated by processing speed, which is associated with lower functional connectivity in the bilateral lateral PFC when these individuals apply learned rules to solve novel problems.
RESUMO
Individuals with autism spectrum disorder (ASD) perform poorly in working memory (WM) tasks, with some literature suggesting that their impaired performance is modulated by WM load. While some neuroimaging and neurophysiological studies have reported altered functional connectivity during WM processing in individuals with autism, it remains largely unclear whether such alterations are moderated by WM load. The present study aimed to examine the effect of WM load on functional connectivity within the prefrontal cortex (PFC) in ASD using functional near-infrared spectroscopy (fNIRS). Twenty-two children with high-functioning ASD aged 8-12 years and 24 age-, intelligent quotient (IQ)-, sex- and handedness-matched typically developing (TD) children performed a number n-back task with three WM loads (0-back, 1-back, and 2-back). Hemodynamic changes in the bilateral lateral and medial PFC during task performance were monitored using a multichannel NIRS device. Children with ASD demonstrated slower reaction times, specifically during the "low load" condition, than TD children. In addition, the ASD and TD groups exhibited differential load-dependent functional connectivity changes in the lateral and medial PFC of the right but not the left hemisphere. These findings indicate that WM impairment in high-functioning ASD is paralleled by load-dependent alterations in right, but not left, intrahemispheric connectivity during WM processing in children with ASD. A disruption of functional neural connections that support different cognitive processes may underlie poor performance in WM tasks in ASD.
Assuntos
Memória de Curto PrazoRESUMO
Various proteins in the endometrial epithelium are differentially expressed in the receptive phase and play a pivotal role in embryo implantation. The Protein Disulphide Isomerase (PDI) family contains 21 members that function as chaperone proteins through their redox activities. Although total PDIA1 protein expression was high in four common receptive (Ishikawa and RL95-2) and non-receptive (HEC1-B and AN3CA) endometrial epithelial cell lines, significantly higher membrane PDIA1 expression was found in non-receptive AN3CA cells. In Ishikawa cells, oestrogen up-regulated while progesterone down-regulated membrane PDIA1 expression. Moreover, mid-luteal phase hormone treatment down-regulated membrane PDIA1 expression. Furthermore, oestrogen at 10 nM reduced spheroid attachment on Ishikawa cells. Interestingly, inhibition of PDIA1 function by bacitracin or 16F16 increased the spheroid attachment rate onto non-receptive AN3CA cells. Over-expression of PDIA1 in receptive Ishikawa cells reduced the spheroid attachment rate and significantly down-regulated integrin ß3 levels, but not integrin αV and E-cadherin. Addition of reducing agent TCEP induced a sulphydryl-rich microenvironment and increased spheroid attachment onto AN3CA cells and human primary endometrial epithelial cells collected at LH+7/8 days. The luminal epithelial cells from human endometrial biopsies had higher PDIA1 protein expression in the proliferative phase than in the secretory phase. Our findings suggest oestrogen and progesterone regulate PDIA1 expression, resulting in the differential expressions of membrane PDIA1 protein to modulate endometrial receptivity. This suggests that membrane PDIA1 expression prior to embryo transfer could be used to predict endometrial receptivity and embryo implantation in women undergoing assisted reproduction treatment.