The current functional state of local neuronal circuits controls the magnitude of a BOLD response to incoming stimuli.

The purpose of this study was to determine how the history-dependent activation state of neuronal networks controls fMRI signals to incoming stimuli. Simultaneous electrophysiological and blood oxygen level-dependent (BOLD) responses were monitored during stimulation of the perforant pathway with low, high, and again low intensity but, otherwise identical pulse trains. Under three different anesthetics (alpha-chloralose, medetomidine, isoflurane) consecutive low intensity stimulation trains, set just below the threshold for population spike generation to single pulses, yielded a stable BOLD response, although at different magnitudes. The first high intensity train increased the BOLD response under all anesthetics and generated population spikes, with varying amplitudes and latencies (alpha-chloralose, metedomidine) or in a regular pattern (isoflurane). Concurrent to the second high intensity train, the BOLD response became minimal, then slowly increasing with subsequent trains (alpha-chloralose, metedomidine), or immediately rising to a stable level (isoflurane). Second train population spikes became regularized, but at low amplitudes and long latencies that were slowly reversed across trains (alpha-chloralose, medetomidine); while under isoflurane, amplitude and latencies became stabilized with the second train. In comparison to initial stimulation, the final low intensity stimulation trains failed to produce BOLD responses (alpha-chloralose, medetomidine), or left the response unchanged (isoflurane), only reaching stable potentiation of population spikes when under isoflurane. Therefore, the fate of BOLD responses depends on whether a new stable functional state of the intrinsic network can be reached after high intensity stimulation.