When more means less: a paradox BOLD response in human visual cortex

The predictions of the ‘Linear Transfer Model’ (LTM) have been tested only by modulating the frequency of the action potentials while keeping the size of the activated neuronal population constant. The LTM states that the blood oxygenation level-dependent contrast (BOLD) signal is directly proportional to the neuronal activity averaged over milliseconds or seconds. We examined the influence on the BOLD response, of manipulating the size of the activated neuronal population while maintaining the electrical discharge activity constant. We performed functional MR measurements on 30 awake, healthy adult volunteers (15 male and 15 female) using a flashed and reversing checkerboard. These stimuli induced the same vascular response and the same increase in the electrical discharge activity but varied in the size of the neuronal population being activated. The BOLD response measured by the extent of activation and the BOLD signal amplitude, was larger for the flashed than to the reversing checkerboard. An assessment of the local deoxyhemoglobin (HbR) concentration indicated that the neuronal activity was lower during the flashed checkerboard than the reversing checkerboard. Because the checkerboard associated with the lower neuronal activity yielded the larger number of activated voxels and the larger BOLD signal, our results run contrary to the predictions of the ‘Linear Transfer Model’ and for this reason we refer to them as paradoxical. Stimuli defined by luminance contrast or a chromatic contrast yielded identical results. We conclude that the ‘LTM’ may apply to stimuli that modulate the electrical discharge activity but not to stimuli that modulate the size of the activated neuronal population.