Introduction: Attenuation correction (AC) in Single Photon Emission Computed Tomography (SPECT) imaging is a critical factor influencing the accuracy of activity recovery. This study assesses the impact of AC on the quantification of activity in Tc99m-ECD brain SPECT of healthy subjects using Statistical Parametric Mapping (SPM). Materials and Methods: Comparisons between attenuation-corrected (AC) and non-attenuation-corrected (NAC) images were performed using voxel-wise statistical analysis. Data acquisition was carried out using a dual-head gamma camera with iterative reconstruction and corrections for scatter and resolution recovery. Image processing included spatial normalization, smoothing, and paired t-tests using SPM for statistical analysis. Results: The results demonstrate that attenuation correction significantly affects regional activity recovery. Reductions in counts were observed in sub-lobar, extra nuclear, occipital lobe, fusiform gyrus, and inferior parietal lobule. Conversely, increases in counts were detected in more parietal and cerebellar structures such as the inferior and middle frontal gyrus, superior, middle, and inferior temporal gyrus, and inferior and middle occipital gyrus. Conclusion: The findings underscore the importance of attenuation correction in accurately interpreting brain activation patterns. Attenuation correction significantly alters regional activity distribution, improving the accuracy of brain perfusion quantification in SPECT imaging.