Mapping continuous neuronal activation without an ON-OFF paradigm: initial results of BOLD ceiling fMRI

Standard functional magnetic resonance imaging (fMRI) requires alternations between activation (ON) and baseline (OFF) periods to map the haemodynamic response to neuronal activation. Consequently, standard fMRI cannot map continuous activations in conditions like tinnitus without an ON-OFF paradigm. We present a novel approach to fMRI that allows mapping of continuous neuronal activation. Compared with standard fMRI, we introduced the application of CO(2) as potent vasodilator. CO(2) induces a 'global' blood oxygenation level-dependent (BOLD) response. The neurovascular coupling in conjunction with the limited cerebral vasodilation implies a limitation or ceiling of the BOLD response. We hypothesize that active areas exhibit a reduced CO(2)-induced DeltaBOLD due to pre-existing 'local' task-induced BOLD response. This putative reduction in DeltaBOLD might be exploited for mapping of continuous neuronal activation. BOLD ceiling fMRI was tested in the auditory system. Six healthy subjects performed three runs: only continuous monaural auditory; only 10% CO(2); simultaneous auditory and CO(2) stimulation. First, we demonstrated the ceiling of DeltaBOLD during continuous auditory activation. According to the known predominantly contralateral auditory processing, monaural auditory stimulation reduced predominantly contralateral (0.41 +/- 0.13%; P < 0.00001) and significantly less (P < 0.0001) ipsilateral DeltaBOLD (0.33 +/- 0.17%; P < 0.00001). The non-auditory area was not affected. Second, this BOLD ceiling was exploited to generate an initial activation map of continuous auditory activation (ON period). In contrast to standard fMRI, an OFF period without neuronal activation was not required. BOLD ceiling fMRI is proposed as a complement to standard fMRI for those conditions where ON-OFF paradigms are impossible.