Alterations in resting state connectivity along the autism trait continuum: a twin study.

Autism spectrum disorder (ASD) has been found to be associated with alterations in resting state (RS) functional connectivity, including areas forming the default mode network (DMN) and salience network (SN). However, insufficient control for confounding genetic and environmental influences and other methodological issues limit the generalizability of previous findings. Moreover, it has been hypothesized that ASD might be marked by early hyper-connectivity followed by later hypo-connectivity. To date, only a few studies have explicitly tested age-related influences on RS connectivity alterations in ASD. Using a within-twin pair design (N=150 twins; 8-23 years), we examined altered RS connectivity between core regions of the DMN and SN in relation to autistic trait severity and age in a sample of monozygotic (MZ) and dizygotic (DZ) twins showing typical development, ASD or other neurodevelopmental conditions. Connectivity between core regions of the SN was stronger in twins with higher autistic traits compared to their co-twins. This effect was significant both in the total sample and in MZ twins alone, highlighting the effect of non-shared environmental factors on the link between SN-connectivity and autistic traits. While this link was strongest in children, we did not identify differences between age groups for the SN. In contrast, connectivity between core hubs of the DMN was negatively correlated with autistic traits in adolescents and showed a similar trend in adults but not in children. The results support hypotheses of age-dependent altered RS connectivity in ASD, making altered SN and DMN connectivity promising candidate biomarkers for ASD.

[The default mode network: cognitive role and pathological disturbances]. / Le réseau cérébral par défaut : rôle cognitif et perturbations dans la pathologie.

INTRODUCTION: A "resting state" or "default mode network" has been highlighted in functional neuroimaging studies as a set of brain regions showing synchronized activity at rest or in task-independent cognitive state. STATE OF THE ART: A considerable and increasing number of studies have been conducted over the last few years so as to unravel the cognitive function(s) of this brain network. PERSPECTIVES: This review gives an overview of anatomical, physiological and phenomenological data regarding the default mode network. Different hypotheses have been proposed regarding the role of this network. Several studies have highlighted its involvement in autobiographical memory, prospection, self, attention, and theory of mind. The influence of the attention level and consciousness onto resting state brain network activity has also been discussed. Specific changes have been described in normal aging, Alzheimer's disease (AD) and multiple sclerosis (MS). CONCLUSIONS: These studies altogether contribute to a better definition of the default mode network, in terms of implicated brain structures, subtending mechanisms, and potential cognitive roles. For instance, similarities and relationships were found between self-related brain activity and resting-state activity in regions belonging to this network, namely posterior cingulate and prefrontal areas that may reflect introspective activity experienced, more or less consciously, when the brain is not specifically engaged in a cognitive task. As a whole, the default mode network appears as a non human-specific intrinsic functional network, active all over the life from birth until aging where it is progressively modified, and sensitive to different pathologies including AD and MS. On the other hand, many points remain to be clarified concerning this network, such as the exact part of its activity dedicated to self-related cognitive processes (introspection, imaginary mental scenario based on past autobiographical experiences) and that involved in a sentinel-like attentional process designated to react to possible environmental events. Indeed, it seems that this network is functional even in case of low level of consciousness, i.e., during light sleep. Conversely, a loss of self and environment perception as in coma, deep sleep or anesthesia might modulate its connectivity along the anteroposterior axis, i.e., frontal activity disappearance associated with a parietal reinforcement of connectivity. Since studies aiming at highlighting these points are still uncommon to date, exhaustive and objective explorations are needed to better understand all these resting state processes.

Urethral closure mechanisms during sneezing-induced stress in anesthetized female cats.

During stress-induced increase in abdominal pressure, urinary continence is maintained by urethral closure mechanisms. Active urethral response has been studied in dogs and rats. Such an active urethral response is also believed to occur in humans during stress events. We aimed to investigate urethral closure mechanisms during sneezing in cats. Urethral pressures along the urethra (UP1-UP4), with microtip transducer catheters with UP4 positioned in the distal urethra where the external urethral sphincter (EUS) is located, and intravesical pressure were measured, and abdominal wall, anal sphincter (AS), levator ani (LA), and EUS electromyograms (EMGs) were recorded during sneezing under closed-abdomen and open-abdomen conditions in eight anesthetized adult female cats. Proximal and middle urethral response induced by sneezing was not different from bladder response. Distal urethral response was greater compared with proximal and middle urethral and bladder response. In the open-abdomen bladder, proximal and middle urethral responses were similarly decreased and distal urethral response was unchanged compared with the closed-abdomen bladder. Bladder and urethral responses were positively correlated to sneeze strength. EUS, LA, and AS EMGs increased during sneezing. No urine leakage was observed, regardless of the strength of sneeze. In cats urethral closure mechanisms are partly passive in the proximal and middle urethra and involve an active component in the distal urethra that is believed to result from EUS and possibly LA contractions. Because central serotonin exerts similar effects on the lower urinary tract in cats and humans, the cat may represent a relevant model for pharmacological studies on continence mechanisms.