Stimulus dependence of oxygenation-sensitive MRI responses to sustained visual activation G. Kru È ger, A. Kleinschmidt and J. Frahm* Biomedizinische NMR Forschungs GmbH am Max-Planck-Institut fu È r biophysikalische Chemie, D-37070 Go È ttingen, Germany Received 8 July 1997; revised 24 September 1997; accepted 25 November 1997 ABSTRACT: Oxygenation-sensitive MRI responses to repetitive and sustained visual activation were compared for stimuli with different temporal, spatial, and luminance contrasts, i.e. reversing checkerboard, flashing diffuse red light, and stationary diffuse gray light with darkness as a control. All paradigms elicited an initial oxygenation ‘overshoot’ as well as a post-stimulus ‘undershoot’. However, whereas flashing and stationary diffuse light resulted in more than a 50% decrease of the initial signal response after 6 min of stimulation, checkerboard responses remained largely unaffected (less than 20% signal attenuation). The demonstration of a stimulus dependence for sustained visual activation reconciles apparently contradictory reports for stimuli involving checkerboards as opposed to goggles, flickerlight, and movies. It may be caused by stimulus-dependent adjustments of neuronal activity, oxygen consumption, blood flow, or blood volume.  1998 John Wiley & Sons, Ltd. KEYWORDS: human brain; functional anatomy; visual responses; magnetic resonance imaging; oxidative metabolism INTRODUCTION Magnetic resonance imaging (MRI) sensitized to changes in cerebral blood oxygenation (CBO) allows mapping of human brain activation in response to functional challenge. It is based on the detection of stimulus-related magnetic field alterations that are caused by changes in the absolute concentration of paramagnetic deoxyhemo- globin (deoxy-Hb). In relation to a focal change in neuronal activity, deoxy-Hb levels reflect the interplay of adjustments in blood flow, blood volume, and oxygen metabolism. Because pertinent phenomena may well exhibit different time constants, the temporal evolution of functional CBO contrast depends not only on the timing of the measuring protocol, but also on the design of the actual paradigm. Previous investigations of prolonged visual stimula- tion with binocular LED goggles, 1 flickering light patterns, 2 checkerboard stimuli, 3 and movie presenta- tions 4 yielded inconsistent findings with reference to a decrease of the initial CBO-sensitive MRI signal response during stimulation periods of several minutes. Whereas technical differences between FLASH and EPI sequences could be ruled out as a potential source of differences in temporal response functions, 5,6 we re- ported a system dependence of the long-term CBO behavior in that visual but not motor activation displayed a gradual attenuation of the MRI signal response. 7 Here we extend this concept and hypothesize that even within a given brain system the hemodynamic and/or metabolic responses to functional activation depend on stimulus features and result in different CBO–MRI response profiles. The stimuli investigated involved those commonly applied in brain mapping as well as in electrophysiologic and psychophysic studies, i.e. a reversing black and white checkerboard, flashing diffuse red light, and stationary diffuse gray light. A preliminary account of part of this work has been given in abstract form. 8 METHODS All studies were conducted at 2.0 T (Siemens Vision, Erlangen, Germany) using the standard imaging headcoil. A total of seven healthy subjects (age 25–33 years, mean 28 years) were examined in 10 sessions by dynamic CBO-sensitive MRI sequences (RF spoiled FLASH, TR/ TE = 62.5/30 ms, flip angle 10°) yielding spin-density weighted images with T 2 * sensitivity (6.0 s temporal resolution, 96 Â 256 matrix, 150 Â 200 mm 2 rectangular NMR IN BIOMEDICINE NMR Biomed 11, 75–79 (1998) *Correspondence to: Biomedizinische NMR Forschungs GmbH am Max-Planck-Institut fu ¨r biophysikalische Chemie, D-37070 Go ¨ttingen, Germany. Abbreviations used: CBO, cerebral blood oxygenation; CMRO2, cerebral metabolic rate of oxygen; EPI, echo-planar imaging; FLASH, fast low angle shot; Hb, hemoglobin; MRI, magnetic resonance imaging; PET, positron emission tomography; RF, radiofrequency; TE, echo time; TR, repetition time.  1998 John Wiley & Sons, Ltd. CCC 0952–3480/98/020075–05 $17.50