A collaborative study by the University of Basque Country and the University of Nottingham has managed to identify the structural damage to the brain by chronic excessive alcohol use. The study is the first of its kind and details the damage at the molecular level.
The structural damage is in the areas associated with executive functioning such as planning, strategic thinking, working memory, selective attention and control of behavior or impulse control. The research was published in the PLOS ONE journal and points conclusively to structural damage in the prefrontal area of the brain.
The study consisted of analyzing the postmortem brains of 20 people previously diagnosed with alcohol abuse/dependence and 20 non-alcoholic brains. The specific regions affected include the α- and β-tubulin and the β II spectrin proteins, which significantly altered the neuronal structure in the brain of acoholic patients. Optical microscopy revealed that the neurons in the prefrontal regions of the brains of the alcoholic patients had undergone alterations compared to those of non-alcoholic patients.
Next the researchers used proteomic techniques in order to identify which specific proteins were modified in these neurons. Tubulins are globular proteins, whereas spectrins are responsible for maintaining the cell shape. In order to quantify the amount of protein in each brain sample the Western Blot technique was used, and determined that the level of protein was reduced as a consequence of the damage produced by ethanol. Mass spectrometry, identified the exact nature of the proteins affected and confirmed that within the tubulin protein family there was a reduction in the α and β proteins; while among the spectrins, there was a decrease in the β II protein.
A previous study had detected changes in executive function in living alcoholic individuals who were subjected to a series of testing to measure their cognitive skills. The results of the study will be published in July 2014, in the online issue of Alcoholism, and analyzed the impact on three networks involved in brain functioning: altering, orienting and executive control. Deficits in executive control were severely pronounced.
In this study 30 sober and detoxified alcohol dependent individuals were recruited as well as 30 individuals who drank lightly. The subjects were matched for age, gender and education. The research participants completed the Attention Network Test designed to examine changes related to the three intentional network described above. The alcohol dependent individuals had substantial difficulties resolving task conflicts and the deficits were found at the higher level of attentional network called executive control, specifically, executive functions and frontal lobe functioning. The deficits were related to the direct effects of the duration and intensity of AD on the frontal regions of the brain.
“Excessive drinking has a negative impact on brain structure and functioning, leading to neuronal loss and impaired functioning of several brain areas, particularly the frontal lobe or the anterior part of the brain, that is the prefrontal and frontal areas,” said Pierre Maurage, a professor at the Université catholique de Louvain as well as corresponding author for the study.
“These areas are notably responsible for higher cognitive functions, like the ability to plan, adapt or inhibit our behaviors according to changes in our environment. AD can impair these high-level cognitive functions, leading to maladapted behaviors, particularly an inability to inhibit alcohol consumption behaviors.”
“Attention is of course a fundamental process of human cognition,” said Salvatore Campanella, professor of psychopathology at the University of Brussels, and research associate at the Belgian Fund of Scientific Research. “Moreover, it is true that attention may be subdivided in several sub-components, implemented in partially different neural networks. Therefore, investigating which attentional mechanisms are specifically affected by alcohol consumption is highly relevant at the clinical level, as different forms of attentional disabilities may be differently rehabilitated.”
“While earlier studies had described globally impaired attentional abilities in AD on the basis of unspecific tasks,” said Maurage, “we found that attention is not globally impaired in AD. Indeed, two attentional networks — alerting and orienting — present preserved functioning in AD, while deficits were found at the higher level of attentional network called executive control, specifically, executive functions and frontal lobe functioning. Importantly, this deficit seems related to the direct effects of the duration and intensity of AD on the frontal regions of the brain.”
“In summary,” added Campanella, “attentional abilities are not all affected by alcohol consumption. The main problem induced by long-term alcohol abuse is an inability to detect and resolve the conflict between task-relevant stimulus and interference provoked by task-irrelevant stimuli: in other words, alcoholics have difficulties in engaging attention on pertinent stimuli, and disengaging attention from non-pertinent stimuli.”
“Practically speaking, this means that the ability to correctly react and to orient one’s attention to stimulations present in the environment, which is a crucial ability for everyday life, is still present in AD, but these attentional abilities are not correctly used because the deficit in executive control hampers the adaptive and efficient use of them,” said Maurage. “At the clinical level, it also shows that therapeutic programs should not focus on the rehabilitation of basic attentional features, because they are actually preserved, but rather on high-level executive functions like inhibition or impulsivity control in order to improve attention.”
The researchers recommend that therapeutic programs should be used to rehabilitate specifically impaired abilities, improving executive control and reducing the risk of relapse.
Pierre Maurage, Philippe de Timary, Joël Billieux, Marie Collignon, Alexandre Heeren. Attentional Alterations in Alcohol Dependence Are Underpinned by Specific Executive Control Deficits. Alcoholism: Clinical and Experimental Research, 2014; DOI: 10.1111/acer.12444
Amaia M. Erdozain, Benito Morentin, Lynn Bedford, Emma King, David Tooth, Charlotte Brewer, Declan Wayne, Laura Johnson, Henry K. Gerdes, Peter Wigmore, Luis F. Callado, Wayne G. Carter. Alcohol-Related Brain Damage in Humans. PLoS ONE, 2014; 9 (4): e93586 DOI: 10.1371/journal.pone.0093586