Transients, such as adaptation of the positive response and the post-stimulus undershoot, are common features of the BOLD response¹. Their origins can be linked to both active mechanisms induced by changes in neuronal activity² and to passive mechanisms resulting from vascular³ or/and metabolic uncoupling⁴. The aim of this study is to investigate the dependence of both active and passive mechanisms underlying BOLD response transients on stimulus type and echo-time (TE).⁵ Being able to disentangle active and passive mechanisms from TE dependency of the BOLD response may provide an additional window for studying the physiological origins of the BOLD response.Subjects (n=2) performed six runs of passive visual task, each 715 s long. Within each run, we alternated between static and reduced-contrast flickering (4 Hz) checkerboard conditions (both 55 s long), interleaved with resting periods (110 s long). Functional data were acquired on a Siemens 3T Magnetom Prisma scanner with multi-echo GE-EPI sequence⁶ with the following parameters: TE1/2/3/4/5/6 = 8/21/33/46/58/71 ms and TR = 1100 ms, voxel size = 3 mm isotropic. Additionally, we acquired T1-weighted (MPRAGE, 1 mm isotropic) anatomical data. Activated voxels (p<0.05; FWE corrected; restricted to gray matter) from left and right V1, based on BOLD data with TE = 33 ms, were used to generate ROIs for quantitative analysis of the six-TE data. The average percent signal change time courses were plotted for six TEs and for both static and flickering conditions. Next, to visualize the effect of TE on BOLD response transients over time, we normalized all responses to the amplitude of the BOLD response at t = 18 s. Finally, to evaluate differences between two conditions independent of TE effect, we used a linear model of (the non-normalized) percent signal change ($$$\triangle S/S=-\triangle R_2^*\times TE+intercept$$$) and fitted at early (t = 18 s) and late (t = 58 s) phases of positive BOLD responses and at early phase of the post-stimulus BOLD undershoot (t = 72 s).The amplitudes of the positive BOLD response and post-stimulus BOLD undershoot in both stimulus conditions increase linearly with TE (see Fig.1). However, there are significant differences in the responses to static and flickering conditions. During the static condition, the positive BOLD responses reach their peaks at 18 s and then decline during the stimulation period. The magnitude of the decline from the peak is dependent on TE: amplitude difference between the peak and the end of stimulation increases with TE (see Fig.2). There is no significant post-stimulus undershoot in the BOLD response with the shortest TE, but it becomes more pronounced with higher TE. During the flickering condition, the positive responses continue to rise after 18 s until they reach a steady-state plateau (see Fig.2). This increase is least­ for the shortest TE and maximal for the longest TE. The post-stimulus undershoot for flickering stimulus is significant even with the shortest TE and scales linearly with increasing TE. Differences between static and flickering conditions and also for different time points of the BOLD response are described by regression analysis (Fig.3). The slope of the fitted line is almost identical between static and flickering conditions in the early phase of positive response (110 and 111 s^-1, respectively). In the late phase, the slope is smaller for static stimulus (72 s^-1) compared to flickering stimulus (110 s^-1). Finally, for the post-stimulus BOLD undershoot after static stimulus the slope is about half (-29 s^-1) of that after flickering stimulus (-72 s^-1).We demonstrate that the BOLD response transients can be modulated by both stimulus type and echo-time. First, we confirmed previous results² that the post-stimulus undershoot can be varied independently of the positive BOLD response amplitude. In addition, TE modulates the response transients differently over time. Differences in the slopes suggest that different physiological mechanisms operate at different phases of the BOLD signal. That is, for a pure susceptibility (i.e. blood oxygenation) change but with different amplitudes, it is expected that the slope of the amplitude vs. TE remains the same. Therefore, differences in the slope indicate either time-varying mismatch between CBF and CBV or between CBF and CMRO₂. We, therefore, suggest that TE dependence of the BOLD signal provides additional information on the underlying physiological mechanisms and, thus, provides a window for studying brain physiology. We are currently evaluating biophysical BOLD signal models in order to disentangle neuronal and vascular mechanisms from multi-echo data.