Application of multi-pinhole collimator in pinhole-based SPECT increases detection sensitivity. The presence of multiplexing in projection images due to the usage of multiple pinholes can further improve the sensitivity at the cost of adding data ambiguity. We are developing a next-generation adaptive brain-dedicated SPECT system -AdaptiSPECT-C. The AdaptiSPECT-C can adapt the multiplexing level and system sensitivity using adaptable pinhole modules. In this study, we investigated the performance of 4 data acquisition schemes with different multiplexing levels and sensitivities on cerebral SPECT imaging. Schemes #1, #2, and #3 have < 1%, 67%, and 31% overall multiplexing, respectively, while the 4th scheme without multiplexing is considered as ground truth. The ground-truth and schemes #1-3 have 1.0, 1.7, 5.1, and 4.0 times higher sensitivity, respectively, compared to a dual-headed parallel-hole SPECT system at matched spatial resolution. A customized XCAT brain perfusion digital phantom emulating the distribution of I-123 N-isopropyl iodoamphetamine (IMP) in a 99th percentile size male was used for simulations. Data acquisition for each scheme was performed at two count levels (low-count and high-count relative to the recommended clinical count level). The normalized root-mean-square error (NRMSE) for schemes #1, #2, and #3 with the low-count (high-count) scenario showed 11%, 4%, and 5% (10%, 5%, and 6%) deviation, respectively, from that of the multiplex-free ground truth. For both the low-count and high-count scenarios, scheme #1 resulted in the least accurate activity ratio (AR) for almost all the analyzed gray-matter brain regions. Further schemes #2 or #3 led to the most accurate AR values with both low-count and high-count scenarios for all the analyzed gray-matter regions. It was thus observed that even with this large head size which leads to significant multiplexing levels, the higher sensitivity from multiplexing could to some extent mitigate the data ambiguity and be translated into reconstructed images of higher quality.