Does functional MRI detect activation in white matter? A review of emerging evidence, issues, and future directions

Right now your doctor has no clue as to how much damage is in your white matter. With no diagnosis of damage there can be no idea of what stroke protocols work in correcting such damage. You doctor is totally flying blind when trying to determine what needs to be done. But then that is no different that what occurs today in any therapy given to help survivors recover. Everything in stroke is flying blind, no wonder only 10% fully recover. Would you want a blind doctor operating on clipping your aneurysm in your brain? 

http://journal.frontiersin.org/Journal/10.3389/fnins.2014.00239/full? 

Jodie R. Gawryluk^1†, Erin L. Mazerolle^2† and Ryan C. N. D'Arcy^3,4*

• ¹Division of Medical Sciences, Department of Psychology, University of Victoria, Victoria, BC, Canada
• ²Department of Radiology, Faculty of Medicine, University of Calgary, Calgary, AB, Canada
• ³Applied Sciences, Simon Fraser University, Burnaby, BC, Canada
• ⁴Fraser Health Authority, Surrey Memorial Hospital, Surrey, BC, Canada

Functional magnetic resonance imaging (fMRI) is a non-invasive technique that allows for visualization of activated brain regions. Until recently, fMRI studies have focused on gray matter. There are two main reasons white matter fMRI remains controversial: (1) the blood oxygen level dependent (BOLD) fMRI signal depends on cerebral blood flow and volume, which are lower in white matter than gray matter and (2) fMRI signal has been associated with post-synaptic potentials (mainly localized in gray matter) as opposed to action potentials (the primary type of neural activity in white matter). Despite these observations, there is no direct evidence against measuring fMRI activation in white matter and reports of fMRI activation in white matter continue to increase. The questions underlying white matter fMRI activation are important. White matter fMRI activation has the potential to greatly expand the breadth of brain connectivity research, as well as improve the assessment and diagnosis of white matter and connectivity disorders. The current review provides an overview of the motivation to investigate white matter fMRI activation, as well as the published evidence of this phenomenon. We speculate on possible neurophysiologic bases of white matter fMRI signals, and discuss potential explanations for why reports of white matter fMRI activation are relatively scarce. We end with a discussion of future basic and clinical research directions in the study of white matter fMRI.

Motivation to Investigate White Matter fMRI

Functional magnetic resonance imaging (fMRI) is used to visualize the neuroanatomical regions associated with brain function. The most commonly used technique for fMRI, blood oxygenation level dependent (BOLD) contrast, was first demonstrated in the early 1990s (Ogawa et al., 1992). Since then, fMRI has broadened our understanding of how the brain functions under both healthy and diseased conditions (e.g., Rosen et al., 1998; Dolan, 2008; Haller and Bartsch, 2009; Rosen and Savoy, 2012). Although fMRI continues to grow in popularity in both research and clinical settings, the full potential of this technique remains untapped because fMRI activity has historically not been considered to be detectable in white matter tissue (Logothetis and Wandell, 2004). In spite of this, fMRI studies often produce activation in white matter and consequently there has been much debate over whether this activation is a true or false representation of underlying neural activity. There are two main reasons that white matter fMRI is controversial. First, BOLD signal relies on cerebral blood volume and flow, which are three to seven times lower in white matter (Rostrup et al., 2000; Preibisch and Haase, 2001; Helenius et al., 2003). However, the vasculature and perfusion of white matter (Figure 1) are capable of supporting hemodynamic changes that are detectable with BOLD fMRI [see Section White Matter Vasculature, Cerebral Blood Flow (CBF), and Cerebral Blood Volume (CBV)]. Second, the primary source of fMRI signal is thought to arise from post-synaptic potentials (which occur mainly in gray matter) as opposed to action potentials (e.g., Logothetis et al., 2001; but see e.g., Smith et al., 2002). However, neither of these statements exclude the possibility, and there is no direct evidence against the possibility of measuring fMRI activation in white matter.

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