Neurocircuitry of emotion and cognition in alcoholism: Contributions from white matter fiber tractography

Neuroscience Program, SRI International, Menlo Park, California, USA.
Dialogues in clinical neuroscience 12/2010; 12(4):554-60.
Source: PubMed


Chronic alcoholism is characterized by impaired control over emotionally motivated actions towards alcohol use. Neuropathologically, it is associated with widespread brain structural compromise marked by gray matter shrinkage, ventricular enlargement, and white matter degradation. The extent to which cortical damage itself or cortical disconnection by white matter fiber pathway disruption contribute to deficits in emotion, cognition, and behavior can be investigated with in vivo structural neuroimaging and diffusion tensor imaging (DTI)-based quantitative fiber tracking. Tractography in alcoholism has revealed abnormalities in selective white matter fiber bundles involving limbic fiber tracts (fornix and cingulum) that connect cortico-limbic-striatal nodes of emotion and reward circuits. Studies documenting brain-behavior relationships support the role of alcoholism-related white matter fiber degradation as a substrate of clinical impairment. An understanding of the role of cortico-limbic fiber degradation in emotional dysregulation in alcoholism is now emerging.

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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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    • "The OFC is a PFC subdivision heavily involved in the regulation of emotion and decision-making, which are dysfunctional in both alcoholism and major depression (Austin et al., 2001; Dom et al., 2005; Drevets, 2007; Volkow and Fowler, 2000). In addition, structural and functional neuroimaging studies have revealed significant abnormalities in the OFC in depression and alcoholism (Dom et al., 2005; Drevets, 2007; Schulte et al., 2010). "
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    ABSTRACT: Reduced density of glial cells and low levels of some astrocyte proteins have been described in the orbitofrontal cortex (OFC) in depression and alcoholism, two disorders often comorbid. These regressive changes may also involve the communication between astrocytes via gap junctions and hemichannels, which play important regulatory roles in neurotransmission. We determined levels and morphological immunostaining parameters of connexin 43 (Cx43), the main protein subunit of astrocyte gap junctions/hemichannels, in the OFC of subjects with depression, alcoholism or comorbid depression/alcoholism as compared to non-psychiatric subjects. Postmortem brain samples from 23 subjects with major depressive disorder (MDD), 16 with alcohol dependence, 13 with comorbid MDD and alcohol dependence, and 20 psychiatrically-normal comparison subjects were processed for western blots to determine Cx43 levels. Area fraction of Cx43 immunoreactivity, and density and average size of immunoreactive puncta were measured in histological sections. There was a significant, larger than 60 percent decrease in Cx43 level in the three psychiatric groups as compared to controls. Area fraction of immunoreactivity and immunoreactive punctum size were reduced in all psychiatric groups, but Cx43-immunoreactive puncta density was reduced only in alcohol-dependent subjects. Among psychiatric subjects, no difference in Cx43 levels or immunostaining was found between suicides and non-suicides. The present data suggest that dysfunction of the OFC is accompanied by reduction in the levels of gap junction protein Cx43 in depression and alcoholism, and reduction in density of Cx43 immunoreactive puncta only in alcoholism, pointing to altered gap junction or hemichannel-based communication in the pathophysiology of those disorders.
    Full-text · Article · Apr 2014 · Journal of Psychiatric Research
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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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