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BackgroundAccumulating neuroimaging studies in humans have shown that acupuncture can modulate a widely distributed brain network, large portions of which are overlapped with the pain-related areas. Recently, a striking feature of acupuncture-induced analgesia is found to be associated with its long-last effect, which has a delayed onset and gradually reaches a peak even after acupuncture needling being terminated. Identifying temporal neural responses in these areas that occur at particular time -- both acute and sustained effects during acupuncture processes -- may therefore shed lights on how such peripheral inputs are conducted and mediated through the CNS. In the present study, we adopted a non-repeated event-related (NRER) fMRI paradigm and control theory based approach namely change-point analysis in order to capture the detailed temporal profile of neural responses induced by acupuncture.ResultsOur findings demonstrated that neural activities at the different stages of acupuncture presented distinct temporal patterns, in which consistently positive neural responses were found during the period of acupuncture needling while much more complex and dynamic activities found during a post-acupuncture period. These brain responses had a significant time-dependent effect which showed different onset time and duration of neural activities. The amygdala and perigenual anterior cingulate cortex (pACC), exhibited increased activities during the needling phase while decreased gradually to reach a peak below the baseline. The periaqueductal gray (PAG) and hypothalamus presented saliently intermittent activations across the whole fMRI session. Apart from the time-dependent responses, relatively persistent activities were also identified in the anterior insula and prefrontal cortices. The overall findings indicate that acupuncture may engage differential temporal neural responses as a function of time in a wide range of brain networks.ConclusionsOur study has provided evidence supporting a view that acupuncture intervention involves complex modulations of temporal neural response, and its effect can gradually resolve as a function of time. The functional specificity of acupuncture at ST36 may involve multiple levels of differential activities of a wide range of brain networks, which are gradually enhanced even after acupuncture needle being terminated.

Recent neuroimaging studies have shown that the cognitive and memory decline in patients with Alzheimer's disease (AD) is coupled with abnormal functions of focal brain regions and disrupted functional connectivity between distinct brain regions, as well as losses in small-world attributes. However, the causal interactions among the spatially isolated, but functionally related, resting state networks (RSNs) are still largely unexplored. In this study, we first identified eight RSNs by independent components analysis from resting state functional MRI data of 18 patients with AD and 18 age-matched healthy subjects. We then performed a multivariate Granger causality analysis (mGCA) to evaluate the effective connectivity among the RSNs. We found that patients with AD exhibited decreased causal interactions among the RSNs in both intensity and quantity relative to normal controls. Results from mGCA indicated that the causal interactions involving the default mode network and auditory network were weaker in patients with AD, whereas stronger causal connectivity emerged in relation to the memory network and executive control network. Our findings suggest that the default mode network plays a less important role in patients with AD. Increased causal connectivity of the memory network and self-referential network may elucidate the dysfunctional and compensatory processes in the brain networks of patients with AD. These preliminary findings may provide a new pathway towards the determination of the neurophysiological mechanisms of AD.