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

Gawryluk JR, Mazerolle EL, D'Arcy RC - Front Neurosci (2014)

Bottom Line: 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).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.We end with a discussion of future basic and clinical research directions in the study of white matter fMRI.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Sciences, Department of Psychology, University of Victoria Victoria, BC, Canada.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

The vasculature and perfusion of the white matter of the human brain. (A) Capillary density for various layers of the cortex (left panel) compared to white matter (right panel). Fixed human brains were embedded in paraffin, sectioned (10 microns) and stained by means of Goldner's trichrome-method (reproduced with permission; Lierse and Horstmann, 1965). (B) Blood vessels on the surface of the corpus callosum (circled in blue). Photo captured during neurosurgery for corpus callosotomy (photo credit: R. D'Arcy). (C) Detection of white matter perfusion with arterial spin labeling MRI. Cerebral blood flow maps with different scale bars in order to better view gray matter perfusion (left) and white matter perfusion (middle). The right image shows the anatomy for reference (reproduced with permission; Van Osch et al., 2009).
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Figure 1: The vasculature and perfusion of the white matter of the human brain. (A) Capillary density for various layers of the cortex (left panel) compared to white matter (right panel). Fixed human brains were embedded in paraffin, sectioned (10 microns) and stained by means of Goldner's trichrome-method (reproduced with permission; Lierse and Horstmann, 1965). (B) Blood vessels on the surface of the corpus callosum (circled in blue). Photo captured during neurosurgery for corpus callosotomy (photo credit: R. D'Arcy). (C) Detection of white matter perfusion with arterial spin labeling MRI. Cerebral blood flow maps with different scale bars in order to better view gray matter perfusion (left) and white matter perfusion (middle). The right image shows the anatomy for reference (reproduced with permission; Van Osch et al., 2009).

Mentions: 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.


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

Gawryluk JR, Mazerolle EL, D'Arcy RC - Front Neurosci (2014)

The vasculature and perfusion of the white matter of the human brain. (A) Capillary density for various layers of the cortex (left panel) compared to white matter (right panel). Fixed human brains were embedded in paraffin, sectioned (10 microns) and stained by means of Goldner's trichrome-method (reproduced with permission; Lierse and Horstmann, 1965). (B) Blood vessels on the surface of the corpus callosum (circled in blue). Photo captured during neurosurgery for corpus callosotomy (photo credit: R. D'Arcy). (C) Detection of white matter perfusion with arterial spin labeling MRI. Cerebral blood flow maps with different scale bars in order to better view gray matter perfusion (left) and white matter perfusion (middle). The right image shows the anatomy for reference (reproduced with permission; Van Osch et al., 2009).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4125856&req=5

Figure 1: The vasculature and perfusion of the white matter of the human brain. (A) Capillary density for various layers of the cortex (left panel) compared to white matter (right panel). Fixed human brains were embedded in paraffin, sectioned (10 microns) and stained by means of Goldner's trichrome-method (reproduced with permission; Lierse and Horstmann, 1965). (B) Blood vessels on the surface of the corpus callosum (circled in blue). Photo captured during neurosurgery for corpus callosotomy (photo credit: R. D'Arcy). (C) Detection of white matter perfusion with arterial spin labeling MRI. Cerebral blood flow maps with different scale bars in order to better view gray matter perfusion (left) and white matter perfusion (middle). The right image shows the anatomy for reference (reproduced with permission; Van Osch et al., 2009).
Mentions: 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.

Bottom Line: 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).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.We end with a discussion of future basic and clinical research directions in the study of white matter fMRI.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Sciences, Department of Psychology, University of Victoria Victoria, BC, Canada.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus