Effect of Luminance Contrast on BOLD fMRI Response in Human Primary Visual Areas

Bradley G. Goodyear1 and Ravi S. Menon1, 2, 3

1 Department of Medical Biophysics and 2 Department of Diagnostic Radiology and Nuclear Medicine, University of Western Ontario; and 3 Laboratory for Functional Magnetic Resonance Research, John P. Robarts Research Institute, London, Ontario N6A 5K8, Canada

    ABSTRACT
Abstract
Introduction
Methods
Results
References

Goodyear, Bradley G. and Ravi S. Menon. Effect of luminance contrast on BOLD fMRI response in human primary visual areas. J. Neurophysiol. 79: 2204-2207, 1998. In this study, we examined the effect of stimulus luminance contrast on blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging within human visual cortex (V1 and extrastriate). Between experiments, the calibrated luminance of a single red LED covering 2° of the subject's visual field was changed relative to a constant background luminance. This stimulus provided a different foveal luminance contrast for each experiment. We used an echo planar imaging sequence to collect blood-oxygenation-sensitive images during and in the absence of the presented stimulus. Our results showed that within V1 there was an increase in the spatial extent of activation with increasing stimulus contrast, but no trend was seen within extrastriate. In both V1 and extrastriate, the local mean activation level for all activated image pixels remained constant with increasing luminance contrast. However, when we investigated activated pixels common to all luminance contrast levels, we found that there was an increase in the mean activation level within V1, but not within extrastriate. These results suggest that there is an increase in the activity of cells in V1 with increasing luminance contrast.

    INTRODUCTION
Abstract
Introduction
Methods
Results
References

The flow of oxygenated blood increases to areas of the brain that respond to a cognitive task or sensory input (Roy and Sherrington, 1890). In a functional magnetic resonance imaging (fMRI) experiment, areas of functional activity are located by examining intensity differences between blood-oxygenation-sensitive (or T*2-weighted) magnetic resonance images collected during and in the absence of a presented stimulus. This mechanism has been termed blood-oxygenation-level-dependent (BOLD) contrast (Ogawa 1990), and has been widely used, for example, in fMRI studies of photic stimulation of visual cortex (Tootell et al. 1995, 1996). Studies have investigated the effect of the stimulus presentation frequency and flicker frequency on fMRI response (Kwong 1992; Thomas 1997), but little attention has been given to the effect of the luminance of the presented stimulus relative to the background luminance (the stimulus luminance contrast). Experiments using BOLD fMRI have also shown that visual stimuli such as contrast-reversing gratings or checkerboard patterns are better than diffusely illuminated stimuli at eliciting a BOLD fMRI response in primary visual areas, but have not addressed the underlying mechanisms responsible for these findings.

In more sophisticated fMRI experiments, it is common practice to examine activation differences between multiple visual states. A difference in stimulus contrast or luminance between the presentations of a visual stimulus may lead to areas of false activation if the area of the brain under investigation plays a role in the coding of stimulus contrast or luminance. In studies aimed at elucidating the cortical response resulting from individual ocular inputs (e.g., ocular dominance column studies), an imbalance in stimulus contrast or luminance may lead to falsely activated areas that show differences in monocular responses at the cortical level. To avoid this problem, it is important to know if contrast and luminance are coded in the primary visual cortex when designing a visual paradigm for a fMRI study of this area.

Miyaoka et al. (1979) have investigated the uptake of labeled deoxyglucose in V1 of albino rats in response to a diffusely illuminated visual stimulus. In their study, there was no appreciable change in deoxyglucose uptake with increasing luminance. Albrecht and Hamilton (1982) have made measurements of the electrical activity of V1 neurons within cat and monkey cortex in response to changes in local contrast of a visual stimulus. Their results showed that there was an increase in neuronal firing rate (in spikes/s) with increasing stimulus contrast, which was dependent on the spatial frequency of that contrast. In addition, this response saturated when the contrast approached two to three orders of magnitude. To date, studies of contrast-sensitivity in humans have been limited to optical measurements of retina adaptation to stimulus contrast. In these studies, human contrast-sensitivity has been shown to increase with mean field luminance, but saturates at low spatial frequencies (van Nes and Bouman 1967). De Lange (1958) measured temporal contrast sensitivity by using contrast-reversing gratings and found that at high mean field luminance the contrast sensitivity maximized near 8-10 Hz. This has also been shown at the cortical level in V1 studies using position emission tomography (PET) (Fox and Raichle 1984) and fMRI (Kwong 1992). PET studies (Fox and Raichle 1985) have demonstrated that there are no luminance effects on the regional cerebral blood flow for a visual stimuli subtending a large field of view. Their results, however, were restricted by the resolvable image pixel size within their anatomic region of interest, and confounded by the difference in spatial frequency of their two stimuli. Hence there has been no direct measure of local neuronal activity as a function of local stimulus contrast.

Given the robust BOLD effect at a magnetic field strength of 4 Tesla, the current study investigates the effect of stimulus luminance contrast on fMRI response in primary visual areas. We determine the effect of luminance contrast on the spatial extent and level of activation in primary visual and extrastriate areas within T*2-weighted magnetic resonance (MR) images.


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FIG. 1. Blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) activation maps (overlaid on corresponding anatomic image) of visual cortex showing areas exhibiting a positive response (correlation threshold r = 0.40) to a flickering red LED stimulus with a luminance of (a) 0.5, (b) 2.2, (c) 85, and (d) 250 cd/m2. Background luminance was maintained at ambient room darkness. Occipital pole is located at bottom of each image. Regions of interest (ROIs) selected within V1 and extrastriate are outlined in white.

    METHODS
Abstract
Introduction
Methods
Results
References

All experiments were performed on a Varian UNITY INOVA 4 Tesla whole-body imaging system (Varian, Palo Alto, CA; Siemens, Erlangen, Germany) equipped with 25 mT/m actively shielded whole-body gradients. A distributed-capacitance, circular radio frequency (RF) surface coil with a 13-cm diam was placed under the occipital pole of the subject's head to transmit and receive the RF signal. Stimulus-invoked signal changes were produced within primary visual cortex of volunteers by using a 8 mm diameter red LED flickering at 8 Hz. The luminance of the LED was controlled with a GRASS Instruments (Quincy, MA) visual stimulator control box equipped with a potentiometer. The LED was located ~26 cm from the subject's eyes, subtending ~2° of visual field. The effective luminance of the flashing LED was calibrated [in candelas per square meter (cd/m2)] at a distance of 26 cm with a Minolta CS-100 Chroma Meter (Minolta Camera, Japan). The background luminance was held at a constant value equal to the ambient darkness inside the bore of the MR scanner with the room lights extinguished. This stimulus provided local foveal contrast.

An oblique axial plane through the calcarine sulcus was prescribed within a high resolution (256 × 256) FLASH gradient-recalled echo anatomic (T1-weighted) image (Menon 1993). Experiments were performed with a single-slice echo planar imaging (EPI) sequence (128 × 128 resolution, 20 cm field of view,echo time (TE) = 10 ms, repetition time (TR) = 125 ms, and 10 mm slice thickness). Four trials were performed, each with a different, randomly selected, LED luminance (0.5, 2.2, 85, or 250 cd/m2). This provided a different local foveal-contrast stimulus for each trial. Subjects were asked to fixate on the flickering LED stimulus throughout the experiment. Thirty images were collected during both the photic stimulation and dark control periods. This was repeated four times within each trial, giving a total of 240 images per trial. A total of six subjects were used for this study.

Two regions of interest (ROIs) were selected for analysis within each of the obtained EPI images. One ROI encompassed primary visual areas (V1) and the other included only extrastriate areas. Identical ROIs were used for all trials. For each trial, we performed a pixel cross-correlation (r = 0.40) with an expected pixel timecourse by using Stimulate (Strupp 1996) running a Sun SPARCstation 4. The resulting map displayed pixels showing a BOLD response to the presented stimulus. From this map, we determined the number and the mean percentage change in the intensity of these activated pixels within each ROI over the timecourse of each trial. Activated pixels common to all trials were also selected to monitor their mean percentage change with increasing stimulus luminance contrast.

    RESULTS
Abstract
Introduction
Methods
Results
References

Figure 1 shows activation maps overlaid on the corresponding anatomic image for a LED luminance of (a) 0.5, (b) 2.2, (c) 85, and (d) 250 cd/m2. These results are for a single subject. Activated areas (i.e., pixels passing the correlation threshold) lie within visual cortex. Figure 2 shows the number of activated pixels within the selected ROIs as a function of stimulus contrast. The number of activated pixels (i.e., the spatial extent of activation) within the loosely defined V1 increases with increasing stimulus luminance contrast. However this trend is not seen within extrastriate regions. This result has not been shown in past studies. Figure 3a shows the mean percentage change in activated pixel intensity as a function of luminance contrast for the activation maps in Fig. 1. For the pixels within each of the defined ROIs, there is no significant change in the mean activation level with increasing luminance contrast. This agrees with past PET and visual-evoked potential studies (Fox and Raichle 1984, 1985). However our results show an increasing trend in the mean percentage change in activated pixel intensity within V1 for those pixels common to all trials as the stimulus luminance contrast is increased. Moreover, there is an increase in the activation level of pixels common to any one contrast level and all higher contrast levels (not shown). There is no such trend in extrastriate regions. Figure 3b shows the effect of luminance contrast on the mean percentage change of activated pixels in V1 and extrastriate averaged over six subjects.


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FIG. 2. Number of pixels within V1 and extrastriate showing a positive response to LED stimulus for activation maps in Fig. 1. Luminance contrast has been normalized to lowest contrast level to show relative changes in contrast.


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FIG. 3. Mean percentage change in activated pixel intensity within selected ROIs located in V1 and extrastriate for (a) a single subject and (b) 6 subjects. Luminance contrast has been normalized to lowest contrast level and percent change has been shown relative to percent change in lowest contrast trial. black-square and bullet , all pixels activated in defined ROIs for each trial; square  and open circle , only pixels activated at all luminance contrast levels.

As mentioned above, one ROI was selected to encompass V1. Other visual areas (e.g., V2 and V3) may be included within this ROI. Figure 4 is a map of image pixels that exhibited an increasing trend in their mean activation level as the luminance contrast was increased. In addition, these pixel locations were common to all trials for the subject shown in Fig. 1. A pixel was eliminated if it did not show an increase in its mean activation level with each increase in luminance contrast. An average over all trials would provide more pixels in this map, however, this strict criterion still provides an adequate number of pixels to support our findings. It is important to note that all of these pixels lie within the defined ROI, while no pixels are present in higher visual areas outside the ROI. On inspection of Fig. 4, it seems that these pixels showing an increase in mean activation level with increasing luminance contrast may be anatomically specific to V1. Thus our results suggest that neurons in V1 (and possibly V2 and V3) are sensitive to changes in the local contrast within a visual stimulus.


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FIG. 4. BOLD fMRI map (for subject in Fig. 1) showing pixels that are common to all activation maps. These pixels show areas that increase in "activation" with each increase in luminance contrast. Outlined ROI (in white) is identical to that in Fig. 1.

Coding for local contrast has been determined to take place in the visual pathway as early as in the retina (Wandell 1984). The ambient light intensity during the day can vary up to six orders of magnitude. However the range of contrasts in a typical visual scene span only about two orders of magnitude. By coding contrast, neurons projecting from the retina can convey essential information about the retinal image despite enormous variation in the absolute level of light (Wandell 1984). Assuming that the BOLD fMRI response is a direct correlate of neural activity, our results for V1 may suggest that either more neurons are being recruited within the same imaged voxel as contrast is increased or that neurons activated in V1 during low contrast photic stimulation are more highly activated during high contrast photic stimulation. The latter interpretation would agree with previous studies of cat (Tolhurst and Dean 1987) and macaque (DeValois et al. 1982) primary visual cortex. The results of Tolhurst and Dean (1987) also show that the contrast-sensitivity function (a retina adaptation measurement) for the cat can predict simple cell responses in visual cortex. This has not been discussed extensively in the monkey literature. However, the lineshape of Fig. 3 showing the mean percentage change of activated pixels in V1 common to all trials supports human contrast-sensitivity experiments for low spatial frequency contrast-reversing gratings (van Nes and Bouman 1967). Our study is the first to report that human contrast sensitivity measurements may quantitatively predict the response of cells in primary visual areas.

Shapley (1990) showed by using single cell recordings that cells within the magnocellular layers of the macaque lateral geniculate nucleus (LGN) increase their activity with contrast more readily than do parvocellular cells. As MRI field strengths increase, fMRI studies of LGN and other midbrain structures known to be sensitive to contrast or luminance [e.g., the superior colliculus (Miyaoka et al. 1979)] will become more feasible. A visual paradigm designed to probe the response of primary visual areas and these midbrain structures must therefore take luminance and contrast into consideration.

    ACKNOWLEDGEMENTS

  This work was supported in part by a Medical Research Council of Canada (MRC) Operating Grant MT13350, an MRC Salary Award, and National Eye Institute Grant 1R01-EY-11551-01.

    FOOTNOTES

  Address for reprint requests: R. S. Menon, Laboratory for Functional Magnetic Resonance Research, The John P. Robarts Research Institute, PO Box 5015, 100 Perth Dr., London, Ontario N6A 5K8 Canada.

  Received 2 May 1997; accepted in final form 10 October 1997.

    REFERENCES
Abstract
Introduction
Methods
Results
References

0022-3077/98 $5.00 Copyright ©1998 The American Physiological Society