Disruption of Brain White Matter Microstructure by Excessive Intracellular and Extracellular Fluid in Alcoholism: Evidence from Diffusion Tensor Imaging

Pfefferbaum, Adolf; Sullivan, Edith V.

doi:10.1038/sj.npp.1300623

Cited by 197 publications

(144 citation statements)

References 57 publications

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“…In agreement with other rodent (Harsan, et al, 2006) and human (Huisman, et al, 2006;Nakayama, et al, 2006;Persson, et al, 2006;Pfefferbaum & Sullivan, 2005) studies, FA values observed herein were higher in the splenium than the genu, suggesting across-species consistency in white matter microstructural quality. The FA values for the corpus callosum reported here from both ROI and fiber tracking analyses fall within the range of published values in rodents from ROI analysis (range: 32 to 75%) (Guilfoyle, et al, 2003;Harsan, et al, 2006;Nair, et al, 2005;Tyszka, et al, 2006;Verma, et al, 2005).…”

Section: Discussionsupporting

confidence: 78%

In vivo fiber tracking in the rat brain on a clinical 3T MRI system using a high strength insert gradient coil

et al. 2007

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In vivo neuroimaging methods permit longitudinal quantitative examination of the dynamic course of neurodegenerative conditions in humans and animal models and enable assessment of therapeutic efforts in mitigating disease effects on brain systems. The study of conditions affecting white matter, such as multiple sclerosis, demyelinating conditions, and drug and alcohol dependence, can be accomplished with diffusion tensor imaging (DTI), a technique uniquely capable of probing the microstructural integrity of white matter fibers in the living brain. We used a 3T clinical MR scanner equipped with an insert gradient coil that yields an order of magnitude increase in performance over the whole-body hardware to acquire in vivo DTI images of rat brain. The resolution allowed for fiber tracking evaluation of fractional anisotropy (FA) and apparent diffusion coefficients in the genu and splenium of the corpus callosum. A comparison of short (46 min) and long (92 min) acquisition time DTI protocols indicated low but adequate signal-to-noise ratio (SNR=6.2) of the shorter protocol to conduct quantitative fiber tracking enhanced by multiple acquisitions. As observed in human studies, FA in the rat splenium was higher than in the genu. Advantages of this technology include the use of similar user interface, pulse sequences, and field strength for preclinical animal and clinical human research, enhancing translational capabilities. An additional benefit of scanning at lower field strength, such as 3T, is the reduction of artifacts due to main field inhomogeneity relative to higher field animal systems.

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Section: Discussionsupporting

confidence: 78%

In vivo fiber tracking in the rat brain on a clinical 3T MRI system using a high strength insert gradient coil

et al. 2007

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“…As social disturbances are highly involved in relapse (Zywiak et al, 2003;Uekermann and Daum, 2008), our results suggest that this link between frontal alterations and relapse could be partly due to this inability to regulate social problems when frontal areas are damaged; (b) altered frontocingulate functional connectivity. Several studies showed white matter abnormalities in alcohol-dependence (Pfefferbaum and Sullivan, 2005), which are correlated with higher relapse rates (Sorg et al, 2012). This study, being among the first ones to use PPI analyses in alcohol-dependence, extends these previous results by identifying the functional correlates of structural white matter impairments: these impairments notably lead to altered frontocingulate connectivity, hampering the cognitive regulation of social exclusion feelings and potentially increasing relapse risk.…”

Section: Discussionsupporting

confidence: 66%

Disrupted regulation of social exclusion in alcohol-dependence: An FMRI study

Maurage

Joassin

Philippot

et al. 2013

Neurophysiologie Clinique/Clinical Neurophysiology

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Alcohol-dependence is associated with cognitive and biological alterations, and also with interpersonal impairments. Although overwhelming in clinical settings and involved in relapse, these social impairments have received little attention from researchers. Particularly, brain alterations related to social exclusion have not been explored in alcohol-dependence. Our primary purpose was to determine the neural correlates of social exclusion feelings in this population. In all, 44 participants (22 abstinent alcohol-dependent patients and 22 paired controls) played a virtual game ('cyberball') during fMRI recording. They were first included by other players, then excluded, and finally re-included. Brain areas involved in social exclusion were identified and the functional connectivity between these areas was explored using psycho-physiological interactions (PPI). Results showed that while both groups presented dorsal anterior cingulate cortex (dACC) activations during social exclusion, alcohol-dependent participants exhibited increased insula and reduced frontal activations (in ventrolateral prefrontal cortex) as compared with controls. Alcohol-dependence was also associated with persistent dACC and parahippocampal gyrus activations in re-inclusion. PPI analyses showed reduced frontocingulate connectivity during social exclusion in alcohol-dependence. Alcohol-dependence is thus linked with increased activation in areas eliciting social exclusion feelings (dACC-insula), and with impaired ability to inhibit these feelings (indexed by reduced frontal activations). Altered frontal regulation thus appears implied in the interpersonal alterations observed in alcohol-dependence, which seem reinforced by impaired frontocingulate connectivity. This first exploration of the neural correlates of interpersonal problems in alcohol-dependence could initiate the development of a social neuroscience of addictive states.

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“…Thus, the analysis criteria applied in fiber tracking serve as a form of erosion of voxels with a high potential of containing non-white matter signal. The resulting regionally differential increase in water motility with age is likely attributable to age-related increases in extracellular spaces (Sen and Basser, 2005) but cannot currently be definitively discerned in vivo (e.g., Norris et al, 1994;Pfefferbaum and Sullivan, 2005b;Rumpel et al, 1998;Sehy et al, 2002;Silva et al, 2002). It may also reflect breakdown of myelin sheathing, trapping of fluid between thin or lysed sheathes and between fibers and bulbous swelling of oligodendrocytes observed postmortem in normal aging human and nonhuman primates Sethares, 2002, 2003;Peters et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Quantitative fiber tracking of lateral and interhemispheric white matter systems in normal aging: Relations to timed performance

Sullivan

Rohlfing

Pfefferbaum

2010

Neurobiology of Aging

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The integrity of white matter, as measured in vivo with diffusion tensor imaging (DTI), is disrupted in normal aging. A current consensus is that in adults advancing age affects anterior brain regions disproportionately more than posterior regions; however, the mainstay of studies supporting this anterior-posterior gradient is based primarily on measures of the corpus callosum. Using our quantitative fiber tracking approach, we assessed fiber tract integrity of samples of major white matter cortical, subcortical, interhemispheric, and cerebellar systems (11 bilateral and 2 callosal) on DTI data collected at 1.5 T magnet strength. Participants were 55 men (age 20-78 years) and 65 women (age 28-81 years), deemed healthy and cognitively intact following interview and behavioral testing. Fiber integrity was measured as orientational diffusion coherence (fractional anisotropy, FA) and magnitude of diffusion, which was quantified separately for longitudinal diffusivity (λL), an index of axonal length or number, and transverse diffusivity (λT), an index of myelin integrity. Aging effects were more evident in diffusivity than FA measures. Men and women, examined separately, showed similar age-related increases in longitudinal and transverse diffusivity in fibers of the internal and external capsules bilaterally and the fornix. FA was lower and diffusivity higher in anterior than posterior fibers of regional paired comparisons (genu versus splenium and frontal versus occipital forceps). Diffusivity with older age was generally greater or FA lower in the superior than inferior fiber systems (longitudinal fasciculi, cingulate bundles), with little to no evidence for age-related degradation in pontine or cerebellar systems. The most striking sex difference emerged for the corpus callosum, for which men showed significant decline in FA and increase in longitudinal and transverse diffusivity in the genu but not splenium. By contrast, in women the age effect was present in both callosal regions, albeit modestly more so in the genu than splenium. Functional meaningfulness of these age-related differences was supported by significant correlations between DTI signs of white matter degradation and poorer performance on cognitive or motor tests. This survey of multiple fiber systems throughout the brain revealed a differential pattern of age's effect on regional FA and diffusivity and suggests mechanisms of functional degradation, attributed at least in part to compromised fiber microstructure affecting myelin and axonal morphology.

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Disruption of Brain White Matter Microstructure by Excessive Intracellular and Extracellular Fluid in Alcoholism: Evidence from Diffusion Tensor Imaging

Cited by 197 publications

References 57 publications

In vivo fiber tracking in the rat brain on a clinical 3T MRI system using a high strength insert gradient coil

In vivo fiber tracking in the rat brain on a clinical 3T MRI system using a high strength insert gradient coil

Disrupted regulation of social exclusion in alcohol-dependence: An FMRI study

Quantitative fiber tracking of lateral and interhemispheric white matter systems in normal aging: Relations to timed performance

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