Diffusion Tensor Tractography in Mesencephalic Bundles: Relation to Mental Flexibility in Detoxified Alcohol-Dependent Subjects

INSERM, U797 Research Unit Neuroimaging and Psychiatry, IFR49, Orsay, France.
Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology (Impact Factor: 7.05). 08/2008; 34(5):1223-32. DOI: 10.1038/npp.2008.101
Source: PubMed


Components of the corticocerebellar circuit and the midbrain individually play a central role in addictive processes and have been associated with altered volumes and impairment of cognitive flexibility in alcohol-dependent subjects. The microstructure of white matter bundles composing the corticocerebellar network and passing through the midbrain was studied using diffusion tensor imaging in a group of detoxified alcohol-dependent men (n=20) and a group of healthy men (n=24). The relationship between properties of these white matter bundles and cognitive flexibility performance was investigated in alcohol-dependent subjects. Bundles connecting two regions of interest were analyzed using a fiber-tracking quantitative approach, which provided estimates of the fractional anisotropy and the apparent diffusion coefficient, as well as the number of tracked fibers normalized by the volume of regions of interest. Within the bundles running between the midbrain and pons, a mean of 18% fewer fibers per unit volume were tracked in alcohol-dependent men than in healthy controls. In addition, the normalized number of these fibers correlated with the performance in the Trail-Making Test part-B. Even though the alcohol-dependent subjects were detoxified and apparently neurologically intact, their earlier excessive use of alcohol seems to be associated with altered neural microstructure of mesencephalic white matter bundles, which may contribute to their cognitive flexibility impairment.

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Available from: Nikoleta Kostogianni, Mar 21, 2014
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    • "Alcohol is neurotoxic and inflicts damage to the brain, and WM in the prefrontal cortex in particular (Kril et al. 1997; Harper 2007; Yeh et al. 2009). A decline in WM integrity in alcoholdependent (AD) patients has previously been linked to cognitive deficits, including (working) memory, attention and responsiveness to reward (Harris et al. 2008; Chanraud et al. 2009; Pfefferbaum et al. 2010; Schulte et al. 2010, 2012). However, there are no studies that have investigated the relationship between prefrontal WM integrity and cognitive flexibility in a sample of AD subjects and problematic drinkers (PrDs). "
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    ABSTRACT: Cognitive flexibility has been associated with prefrontal white matter (WM) integrity in healthy controls (HCs), showing that lower WM integrity is associated with worse performance. Although both cognitive flexibility and WM integrity have been found to be aberrant in alcohol-dependent (AD) patients, the relationship between the two has never been tested. In this study, we investigated the association between WM tract density and cognitive flexibility in patients with AD (n = 26) and HCs (n = 22). In order to assess the influence of AD severity, we also included a group of problematic drinkers (PrDs; n = 23) who did not meet the AD criteria. Behavioral responses and brain activity during a cognitive flexibility task were measured during functional magnetic resonance imaging. Probabilistic fiber tracking was performed between the dorsolateral prefrontal cortex and the basal ganglia; two crucial regions for task switching. Finally, the task-related functional connectivity between these areas was assessed. There were no signifi-cant group differences in the task performance. However, compared with HCs, AD patients and PrDs showed decreased WM integrity and increased prefrontal brain activation during task switching. Evidence is presented for a compensatory mechanism, involving recruitment of additional prefrontal resources in order to compensate for WM and neural function impairments in AD patients and PrDs. Although present in both alcohol groups, the PrDs were more successful in invoking this compensatory mechanism when compared to the AD patients. We propose that this may therefore serve as a protective factor, precluding transition from problematic drinking into alcohol dependence.
    Full-text · Article · Dec 2014 · Addiction Biology
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    • "Finally, data showing white matter abnormalities in ADI (Chanraud et al., 2009; Yeh et al., 2009; Schulte et al., 2010), which are correlated with higher relapse rates (Sorg et al., 2012), suggest that alcohol-dependence may be associated with disrupted connectivity between visual and affective brain regions. For instance, ADI show microstructural alterations of the cingulate bundle of the limbic system, suggesting possible connectivity impairments between OFC and parietal areas of the dorsal stream as well as amygdala. "
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    ABSTRACT: Emotional visual perception deficits constitute a major problem in alcohol-dependence. Indeed, the ability to assess the affective content of external cues is a key adaptive function, as it allows on the one hand the processing of potentially threatening or advantageous stimuli, and on the other hand the establishment of appropriate social interactions (by enabling rapid decoding of the affective state of others from their facial expressions). While such deficits have been classically considered as reflecting a genuine emotion decoding impairment in alcohol-dependence, converging evidence suggests that underlying visual deficits might play a role in emotional alterations. This hypothesis appears to be relevant especially as data from healthy populations indicate that a coarse but fast analysis of visual inputs would allow emotional processing to arise from early stages of perception. After reviewing those findings and the associated models, the present paper underlines data showing that rapid interactions between emotion and vision could be impaired in alcohol-dependence and provides new research avenues that may ultimately offer a better understanding of the roots of emotional deficits in this pathological state.
    Full-text · Article · Mar 2014 · Frontiers in Human Neuroscience
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    • "FA reflects a complex mixture of tissue properties including coherence of fiber orientation, myelination, and axonal density [15]. Higher FA values may indicate greater coherence of fiber orientation, increased myelination, decreased axon diameter, increased axon density, and amount of intracellular and extracellular fluid [16–18]. Although it is inappropriate to interpret FA as a direct measure of white matter integrity, it does reflect the physical microstructural properties and serves as a starting point for exploring structural connectivity [15]. "
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    ABSTRACT: Many brain imaging studies have demonstrated reductions in gray and white matter volumes in alcoholism, with fewer investigators using diffusion tensor imaging (DTI) to examine the integrity of white matter pathways. Among various medical conditions, alcoholism and post-traumatic stress disorder (PTSD) are two comorbid diseases that have similar degenerative effects on the white matter integrity. Therefore, understanding and differentiating these effects would be very important in characterizing alcoholism and PTSD. Alcoholics are known to have neurocognitive deficits in decision-making, particularly in decisions related to emotionally-motivated behavior, while individuals with PTSD have deficits in emotional regulation and enhanced fear response. It is widely believed that these types of abnormalities in both alcoholism and PTSD are related to fronto-limbic dysfunction. In addition, previous studies have shown cortico-limbic fiber degradation through fiber tracking in alcoholism. DTI was used to measure white matter fractional anisotropy (FA), which provides information about tissue microstructure, possibly indicating white matter integrity. We quantitatively investigated the microstructure of white matter through whole brain DTI analysis in healthy volunteers (HV) and alcohol dependent subjects without PTSD (ALC) and with PTSD (ALC+PTSD). These data show significant differences in FA between alcoholics and non-alcoholic HVs, with no significant differences in FA between ALC and ALC+PTSD in any white matter structure. We performed a post-hoc region of interest analysis that allowed us to incorporate multiple covariates into the analysis and found similar results. HV had higher FA in several areas implicated in the reward circuit, emotion, and executive functioning, suggesting that there may be microstructural abnormalities in white matter pathways that contribute to neurocognitive and executive functioning deficits observed in alcoholics. Furthermore, our data do not reveal any differences between ALC and ALC+PTSD, suggesting that the effect of alcohol on white matter microstructure may be more significant than any effect caused by PTSD.
    Full-text · Article · Nov 2013 · PLoS ONE
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