Development of MRI Techniques for Drug-Abuse Applications

1. 大脑功能状态的时间动态是认知表现的基础

1. Temporal Dynamics of Functional Brain States Underlie Cognitive Performance The functional organization of the human brain adapts dynamically in response to a rapidly changing environment and disruptions in this process have been linked to cognitive deficits. However, the relation of these rapid changes in functional organization to cognitive functioning is not well understood. This study used a graph-based time-frame modularity analysis approach to identify temporally recurrent functional configuration patterns in the neural responses to an n-back task of working memory performed during functional magnetic resonance imaging. Working memory load was manipulated to investigate the functional relevance of the identified brain states. Four distinct brain states were defined by predominant patterns of activation in the task-positive, default-mode, sensorimotor, and visual networks. Escalating working memory load increased both the occurrence of the task-positive state and the probability of transitioning into this state. Simultaneously, the occurrence of the default-mode and sensorimotor states and the probability of these two states transitioning away from the task-positive state both decreased. Further, the task-positive state occurrence rate and the probability of transitioning from the default-mode state back to the task-positive state explained a significant and unique portion of the variance in task performance. The results demonstrate the dynamics of the functional interactions among large well-defined networks that support successful cognitive functioning and provide a reference to understand the cognitive deficits that characterize multiple neuropsychiatric disorders. (Manuscript under review) 2. Simultaneous TMS and fMRI: Aspects of Technical Implementation The simultaneous transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) offers a unique opportunity to non-invasively stimulate brain circuits while simultaneously monitoring changes in brain activity. However, to take advantage of this multimodal technique, some technical aspects need to be overcome. In this work, we evaluated technical issues associated with the setup and utilization of this multimodal tool, such as the use of a large single-channel radio frequency (rf)-coil, and the artifacts induced by TMS when interleaved with the echo-planar imaging (EPI) sequence. We demonstrated that good image quality can be achieved with this rf-coil, and that the adoption of axial imaging orientation in conjunction with a safe interval of 100 ms, between the TMS pulse and imaging acquisition, is a suitable combination to eliminate potential image artifacts when using the combined TMS-fMRI technique in 3 Tesla MRI scanners. (Manuscript under review) 3. Simultaneous TMS and MRI: Aspects of Neural Mechanism of TMS In this study, we used simultaneous TMS and MRI to investigate acute effects of TMS modulation on the brain. An MRI-compatible TMS coil was used to stimulate the left dorsal lateral prefrontal cortex (DLPFC; MNI = -50, 30, 36), while fMRI being acquired to assess the modulatory effects of the stimulation on the whole brain. Preliminary fMRI data showed that the TMS elicited activation in the insula, auditory cortex (due to the TMS acoustic noise), caudate, thalamus, cerebellum, superior medial frontal gyrus, precentral and angular gyrus and decreased activation in the temporal poles, orbital-frontal cortex (OFC), ventral tegmental area and precuneus. Results from Psychophysiological Interactions (PPI) analysis showed a TMS-associated increase in the connectivity with the TMS site in the caudate, anterior cingulate cortex (ACC), cerebellum, parietal, precuneus and occipital areas, but a TMS-associated decrease in the connectivity with the TMS site in the auditory cortex and thalamus. Positive correlation between fMRI activation maps and rsfMRI functional connectivity maps was observed in the thalamus, putamen, cerebellum, ACC, superior medial frontal gyrus, middle frontal gyrus and occipital area, while negative correlation was observed in the temporal pole, cerebellum, OFC, auditory cortex and middle frontal gyrus. A comprehensive analysis and interpretation of the data will be performed upon completion of the data acquisition on all participants. 4. Transcranial Rotating Permanent Magnet Stimulation (TRPMS) TRPMS is a newly developed non-invasive neuromodulation technique. The principle of TRPMS is to generate fast changing magnetic field on the brain surface underneath the stimulator using a rapidly rotating permanent magnet. Although TRPMS is a type of sub-threshold stimulation and cannot directly induce cortex activation, it is demonstrated to be capable of changing cortical excitability. This study is aimed to evaluate the modulatory effect of TRPMS on cortical excitability by using an A-B-A design with TRPMS and fMRI. First, participants undergo a baseline TMS/fMRI session to get a measurement of baseline cortical excitability in the form of single-pulse TMS induced BOLD activation (A). We then conduct an event-related single-pulse TMS/fMRI session, with TMS stimulus at 120% RMT, 50 events with inter-stimulus-interval (ISI) around 16s (16s with random jittering). EMG recording are conducted on the corresponding FDI muscle through this TMS/fMRI session. Next we stimulate the left motor cortex over the hot-spot with the parameter set that has been demonstrated to have enhancement effect of the motor cortex excitability: 20-min application of TRPMS, 100ms duration, 0.2Hz (one stimulus every 5s), total 240 stimuli (B). Then we evaluate the modulatory effect of the TRPMS stimulation by conducting a second TMS/fMRI session, with the identical procedure of the baseline TMS/fMRI session (A). Upon completion of the evaluation on the neuromodulatory effect of TMS on cortical excitability, more specific studies targeting on therapeutic effects of TRPMS can be designed based on its modulation on cortical excitability.