The capability of non-invasively mapping neuronal excitation and inhibition at the columnar level in human is vital in revealing fundamental mechanisms of brain functions. Here, we show that it is feasible to simultaneously map inhibited and excited ocular dominance columns (ODCs) in human primary visual cortex by combining high-resolution fMRI with the mechanism of binocular inhibitory interaction induced by paired monocular stimuli separated by a desired time delay. This method is based on spatial differentiation of fMRI signal responses between inhibited and excited ODCs that can be controlled by paired monocular stimuli. The feasibility and reproducibility for mapping both inhibited and excited ODCs have been examined. The results conclude that fMRI is capable of non-invasively mapping both excitatory and inhibitory neuronal processing at the columnar level in the human brain. This capability should be essential in studying the neural circuitry and brain function at the level of elementary cortical processing unit.

In this work, we exploited the superior capability of high-resolution functional magnetic resonance imaging (fMRI) for functional mapping of ocular dominance layer (ODL) in the cat lateral geniculate nucleus (LGN). The stimulus-evoked neuronal activities in the LGN ODLs associated with contralateral- and ipsilateral-eye visual inputs were successfully differentiated and mapped using both blood-oxygenation-level dependent (BOLD)-weighted and cerebral blood volume (CBV)-weighted fMRI methods. The morphology of mapped LGN ODLs was in remarkable consistency with histology findings in terms of ODL shape, orientation, thickness and eye-dominance. Compared with the BOLD signal, the CBV signal provides higher reproducibility and better spatial resolvability for function mapping of LGN because of improved contrast-to-noise ratio and point-spread function. The capability of fMRI for non-invasively imaging the functional sub-units of ODL in a small LGN overcomes the limitation of conventional neural-recording approach, and it opens a new opportunity for studying critical roles of LGN in brain function and dysfunction at the fine scale of ocular dominance layer.

The relationship between the blood-oxygenation-level dependent (BOLD) signal and its underlying neuronal activity is still inconclusive. The task of completely understanding this relationship has been encumbered not only by the complexity of neuronal responses, but also by nonlinear characteristics of the vascular response that are not correlated to neural activity. Repeated stimuli inducing replicable neural responses led to successively smaller BOLD amplitudes and delayed BOLD onset latencies when inter-stimulus intervals (ISIs) are shorter than 4-6 s, indicating significant nonlinearity between the BOLD signal and the underlying neuronal activity. We have provided evidence that large-vessel BOLD contributions could be the source of the nonlinearity (Zhang, N., Zhu, X.H., Chen, W., 2008b. Investigating the source of BOLD nonlinearity in human visual cortex in response to paired visual stimuli. Neuroimage 43, 204-212). By utilizing the spin-echo (SE) BOLD fMRI method at high magnetic fields to suppress large-vessel BOLD contributions, we found that the BOLD signal from the micro-vascular activity is replicable in response to replicated neuronal activities even at ISIs as short as approximately 1 s, suggesting that the micro-vascular BOLD activity is essentially a linear system. These results indicate that micro-vascular BOLD signals should provide an accurate estimate of the amplitude of neuronal activity changes. Consequently, the findings are important in understanding and resolving the controversy in the neurovascular coupling relationship. In addition, the difference in BOLD response times between macro- and micro-vascular activities demonstrated herein will have a significant impact on functional connectivity and causality studies. Moreover, SE fMRI at high fields, due to its capability of accurately representing the strength of neural activity as well as its previously shown high spatial specificity to activated brain regions, is an ideal choice for mapping brain function and quantifying the stimulus-evoked brain activity noninvasively.

The possible role of oxygen metabolism in supporting brain activation remains elusive. We have used a newly developed neuroimaging approach based on high-field in vivo (17)O magnetic resonance spectroscopic (MRS) imaging to noninvasively image cerebral metabolic rate of oxygen (CMRO(2)) consumption in cats at rest and during visual stimulation. It was found that CMRO(2) increases significantly (32.3%+/-10.8%, n=6) in the activated visual cortical region as depicted in blood oxygenation level dependence functional maps; this increase is also accompanied by a CMRO(2) decrease in surrounding cortical regions, resulting a smaller increase (9.7%+/-1.9%) of total CMRO(2) change over a larger cortical region displaying either a positive or negative CMRO(2) alteration. Moreover, a negative correlation between stimulus-evoked percent CMRO(2) increase and resting CMRO(2) was observed, indicating an essential impact of resting brain metabolic activity level on stimulus-evoked percent CMRO(2) change and neuroimaging signals. These findings provide new insights into the critical roles of oxidative metabolism in supporting brain activation and function. They also suggest that in vivo (17)O MRS imaging should provide a sensitive neuroimaging modality for mapping CMRO(2) and its change induced by brain physiology and/or pathologic alteration.