Humans often accept the status quo when faced with conflicting choice alternatives. However, it is unknown how neural pathways connecting cognition with action modulate this status quo acceptance. Here we developed a visual detection task in which subjects tended to favor the default when making difficult, but not easy, decisions. This bias was suboptimal in that more errors were made when the default was accepted. A selective increase in subthalamic nucleus (STN) activity was found when the status quo was rejected in the face of heightened decision difficulty. Analysis of effective connectivity showed that inferior frontal cortex, a region more active for difficult decisions, exerted an enhanced modulatory influence on the STN during switches away from the status quo. These data suggest that the neural circuits required to initiate controlled, nondefault actions are similar to those previously shown to mediate outright response suppression. We conclude that specific prefrontal-basal ganglia dynamics are involved in rejecting the default, a mechanism that may be important in a range of difficult choice scenarios.hen faced with a complex decision, people tend to accept the status quo, as reflected in the old adage, "When in doubt, do nothing." Indeed, across a range of everyday decisions, such as whether to move house or trade in a car, or even whether to flip the TV channel, there is a considerable tendency to maintain the status quo and refrain from acting (1). One factor driving this status quo bias is the difficulty of the decision process. In supermarkets, for example, there is often an overwhelming choice of different brands for the same product, and consumers may leave the store empty handed because of a difficulty-induced bias toward inaction (2, 3).Here we shed light on the brain mechanisms involved in making difficult decisions involving a status quo. We operationally define a status quo bias as suboptimal acceptance of a default choice option (Fig. 1B). The neural mechanisms involved in overcoming this bias are unknown, but informative parallels can be derived from the effects of treatments for Parkinson's disease. Akinesia, a core symptom of Parkinson's, can be alleviated by disruption of the basal ganglia either by neurosurgical lesions or deep-brain stimulation (DBS) (4, 5). Despite these beneficial therapeutic effects, it is known that DBS of the subthalamic nucleus (STN) in Parkinson's patients can lead to impairments of cognitive control (6-8), suggesting that one of the core functions of the STN is to modulate basal ganglia circuits involved in decision making (9-11). An anatomic "hyperdirect" pathway from medial and lateral prefrontal cortex, previously characterized in primates (12) and humans (13), may mediate cognitive influences on the STN (14-16). Here we tested whether interactions between the frontal cortex and basal ganglia provide candidate mechanisms for how decision difficulty modulates choices involving a status quo.We asked participants to make sensory judgments in the context of a...
Discoveries in the defective molecular composition of the epidermal barrier, such as the epidermal protein filaggrin, in those with atopic eczema (or atopic dermatitis [AD]) have proved crucial in understanding this disease, but its aetiology remains to be fully elucidated. The epidermal barrier is just one interface between the microbial world and our immune system. Recent advances in molecular technology have demonstrated for the first time the true scale of the normal human microbiome and changes seen in disease states. In this review article we discuss the role of the human microbiome in the aetiology and maintenance of AD. The role of Staphylococcus aureus within the skin microbiome is examined, in addition to the role of other bacteria and fungi, identified using novel culture-independent methods. The significant contribution of the gut microbiome and its manipulation via probiotic use is also reviewed. We emphasise that the microbiome of separate systems, including the gut, has a significant role to play in the manifestation of this cutaneous disorder. To date, there has been a lack of studies investigating whether changes to the lung microbiome may play a role in AD. An early interaction between the microbiome and immune system via multiple routes (skin-gut-lung) could feasibly affect the risk of a subsequent development of atopic diseases. When making management decisions for AD patients, clinicians must be mindful of the role of the microbiome.
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