Research On Hemodynamic And Electrophysiological Spontaneous Low-frequency Oscillations In The Brain

With the microelectrode array, laser Doppler flowmetry and optical imaging of intrinsic signals, this dissertation investigated the neuro- hemodynamic mechanism and stimulus-dependent modulation of spontaneous low- frequency oscillations(LFO). Furthermore, the mechanism of the negative hemodynamic response induced by a brief hindlimb electrical stimulation was explored. The neuro-hemodynamic mechanisms of spontaneous LFO and the negative hemodynamic response are important research topics in the category of neurovascular coupling, which are significant to understand the underlying operation mechanism of the brain. The main contents and contributions of this dissertation are summarized as follows:The multimodal observation of spontaneous LFO. Previously, spontaneous LFO were generally examined in the context of hemodynamic parameters. Here, we employed three techniques including the microelectrode array, laser Doppler flowmetry and optical imaging to monitor spontaneous LFO in the anesthetized rat somatosensory and visual cortices. Not only the hemodynamic signals(including total blood volume, deoxyhemoglobin and cerebral blood flow), but also the neural activities including local field potentials and spike trains were recorded. LFO were detected for all three of the components using the multi- taper method. Spontaneous LFO existing in the neural activity may broaden our horizon of slow rhythms in the cerebral cortex. In addition, the microelectrode array and laser Doppler flowmetry were combined for simultaneous recordings, providing the basic condition for studying the neuro- hemodynamic mechanism of spontaneous LFO.The Granger causality analysis of spontaneous LFO. We evaluated the Granger causal relationships of spontaneous LFOs among cerebral blood flow, local field potentials and spike trains in the rat somatosensory and visual cortices using the Granger causal model. Significant Granger causal relationships were observed from local field potentials to cerebral blood flow and from spike trains to cerebral blood flow at approximately 0.1 Hz. Moreover, the Granger directional influence from local field potentials to cerebral blood flow was larger and more significant than that from spike trains to cerebral blood flow. The present results imply that spontaneous LFOs may originate from neural activities especially local field potentials. To the best of our knowledge, the present study is the first to identify Granger causal influences among cerebral blood flow, local field potentials and spike trains and show that spontaneous LFOs carry important Granger causal influences from neural activities to hemodynamic signals. The Granger causal influences discovered from neural activities to cerebral blood flow may have potential value for increasing the probability that f MRI has a neural basis and providing support for resting-state f MRI studies.The spatio-te mporal modulation of spontaneous LFO elicited by the visual stimulation. Research on the spatio-temporal modulation of spontaneous LFO is important for exploring its origin and revealing underlying regulatory mechanisms in the brain. This dissertation employed the optical imaging technique to examine stimulus- modulated LFO in the rat visual cortex. The stimulation was presented monocularly as a flashing light with different frequencies and intensities. It was found that the rhythms of LFO typically accelerated and the phases in different cortical regions tended to be synchronised after stimulation. These phenomena were confined to visual stimuli with specific flashing frequencies and intensities. The acceleration and convergence induced by the flashing frequency were more marked than the intensity. These results demonstrate that spontaneous LFO can be modulated by parameter-dependent flashing lights and indicate the potential value of the visual stimulus paradigm in exploring the origin and function of LFO.Research on the neuro-hemodynamic mechanis m of the negative hemodynamic response. Currently, the negative hemodynamic response has not been extensively investigated, and its underlying nature is highly controversial. Researchers usually interpret the negative hemodynamic response as a decrease of the neural activity, namely the neural deactivation. Here, we employed the optical imaging technique and microelectrode array recordings in the rat cortex to examine the negative hemodynamic response adjacent to the positive hemodynamic response induced by brief hindlimb electrical stimulation. The microelectrode array recordings demonstrated that the neural activity in the negative hemodynamic response areas was unchanged or increased during stimulation, implying that the negative hemodynamic response occurred without neural deactivation. By comparing the temporal dynamics of the negative and positive hemodynamic responses, the “blood stealing” mechanism was considered to be a possible origin. Furthermore, several negative hemodynamic responses could be explained through increased neural activity. Consequently, caution should be exercised when interpreting the negative hemodynamic response as a decrease in neural activity, especially when the negative hemodynamic response is adjacent to the positive hemodynamic response. This study may provide evidence against the neural deactivation theory and enhance our knowledge of the negative hemodynamic response in the cerebral cortex.