Abstract <p>Preoperative mapping of functionally significant (specifically,eloquent) areas of the cerebral cortex using functional magneticresonance imaging (fMRI) enables assessment of their location relative tothe surgical target, allowing for more effective and safe planningof neurosurgical intervention. In this context, areas of increasedfunctional activity during the performance of a specific test taskare typically identified based on data showing an increase in the BOLD(Blood Oxygen Level-Dependent) signal—the so-called positive BOLDresponse. Meanwhile, according to current consensus, the cerebralsupport of any activity relies on the activity of functional neuroanatomicalsystems involving a number of components—structures and brain regionswhose level of functional activity during engagement in an activitycan either increase or decrease. A decrease in the BOLD signal,corresponding in the shape of its time–intensity curve to a mirrorreflection of the positive BOLD response and referred to as thenegative BOLD response, has been described in the literature asan important characteristic of the mechanisms underlying activitysupport. However, this phenomenon has not yet found diagnostic application,which may be due to its multifactorial nature. This review aimsto analyze the role of the negative BOLD response in the implementationof human cognitive and motor functions and to evaluate its potentialfor use during preoperative fMRI-based mapping. Here, we discussesthe possible mechanisms underlying the origin of a negative BOLD response,its relationship with inhibitory processes, and its contributionto the neuronal support of human activity. Approaches to recordingthis phenomenon are also described, specific clinical examples areprovided, and the prospects for its implementation into preoperativediagnostic practice are discussed.</p>