Alcohols Effects on the Brain: Neuroimaging Results in Humans and Animal Models Alcohol Research: Current Reviews

When the person stops drinking, decreased inhibition combined with a deficiency of GABA receptors may contribute to overexcitation throughout the brain. It should be noted that the balance between the inhibitory action of GABA and the excitatory action of glutamate is a major determinant of the level of activity in certain regions of the brain; the effects of GABA and glutamate on withdrawal and brain function are probably interactive (see Valenzuela 1997 for review). There is evidence that the frontal lobes are particularly vulnerable to alcoholism-related damage, and the brain changes in these areas are most prominent as alcoholics age (Oscar-Berman 2000; Pfefferbaum et al. 1997; Sullivan 2000) (see figure 2).

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These advancements also have allowed analysis of the course of brain structural changes through periods of drinking, abstinence, and relapse. Human studies offer a full depiction of the consequences of chronic alcohol exposure but are limited by ethical considerations. That is, rigorous experimentation requires the ability to control for relevant variables such as the premorbid condition of the brain.

Limbic system structure and function

If a person drinks enough, particularly if they do so quickly, alcohol can produce a blackout. Alcohol-induced blackouts are gaps in a person’s memory for events that occurred while they were intoxicated. These gaps happen because alcohol temporarily blocks the transfer of memories from short-term to long-term storage—a process known as memory consolidation—in a brain area called the hippocampus. As adolescents mature, they undergo complex developmental changes, especially in their brains. The widespread changes in the organization and functioning of the brain—which continue into a person’s mid-20s—bring about the cognitive, emotional, and social skills necessary for adolescents to survive and thrive. The nature of these rapid changes may also increase the adolescent brain’s vulnerability to alcohol exposure.

Alcohol and the Adolescent Brain

Results of twin, family, and adoption studies have shown that hereditary factors influence vulnerability to alcoholism (Begleiter and Porjesz 1999; Dick and Foroud 2003; Schuckit et al. 2004; Whitfield et al. 2004). Additionally, the pharmacogenomics of alcohol response is well established, and genetic variants for the principal enzymes of alcohol metabolism are thought to influence drinking behavior and protect against alcoholism (Dickson et al. 2006; Enoch 2003). Convergent evidence supports the view that vulnerability to alcoholism is likely to be due to multiple interacting genetic loci of small to modest effects (Johnson et al. 2006). Mild swelling of astrocytes is proposed as the key event in the pathogenesis of HE (e.g., Takahashi et al. 1991).

As a result, a person may behave impulsively and inappropriately, which may contribute to excessive drinking. Even though structural and functional brain damage is partially reversible after several weeks of abstinence (Crews et al. 2005; Nixon 2006; Rosenbloom et al. 2003), the underlying mechanisms are poorly understood. It is clear, however, that the locus and extent of brain damage, as well as the type and degree of impairment, differ across individuals. Such differences suggest that certain factors increase the likelihood of developing cognitive, sensory, or motor impairments with alcohol misuse. Additionally, overall physical and mental health are important factors, because comorbid medical, neurological, and psychiatric conditions not only can interact to aggravate alcoholism’s effects on the brain and behavior, but they also can contribute to further drinking (Petrakis et al. 2002). In addition to obtaining structural and functional information about the brain, MRI methodology has been used for other specialized investigations of the effects of alcohol on the brain.

Neuroimaging studies that measured gender differences in alcoholics’ brain functioning have yielded contradictory evidence, with some studies showing women to be more susceptible than men to brain impairments, and other studies showing no such distinction. Using functional magnetic resonance imaging (fMRI), Tapert et al. (2001) found decreased activity in parietal and frontal cortex, particularly in the right hemisphere, in alcohol-dependent women during performance of a spatial working memory task. Other studies, however, did not find functional differences based on gender (Wang et al. 1998), or even found that alcohol intoxication decreased brain metabolism in men more than in women as measured with positron emission tomography (PET; Wang et al. 2003). Using structural MRI, Kroft et al. (1991) found that the average ventricular volume in alcoholic women was within the typical range found in MRI studies of nonalcoholic women of similar ages. Another MRI study reported that although age and alcoholism interacted adversely in both sexes, alcoholic men, but not alcoholic women, had abnormal cortical white matter and sulcal volumes compared to same sex healthy comparison groups (Pfefferbaum et al. 2001b).

Furthermore, researchers have hypothesized that the design, conduct, and analysis of a mainstay of animal experiments are questionable (Matthews 2008) and rarely undergo meta-analytical review for consensus (Mignini and Khan 2006; Peters et al. 2006; Pound et al. 2004; Sandercock and Roberts 2002). Estimates of HE are derived from estimates of alcoholic cirrhosis, which can alcohol poisoning range from 8 percent to 20 percent (Bellentani et al. 1997; Mann et al. 2003; Sorensen et al. 1984). Mild HE occurs in up to 80 percent of cirrhotic patients, and overt HE occurs in up to 45 percent of cirrhotic patients (Bajaj 2008; Poordad 2007). One study estimated the incidence of CPM at 0.5 percent among the general population (Newell and Kleinschmidt-DeMasters 1996).

A similar lack of emotional differentiation to facial expressions by alcoholics also was observed in the hippocampus. The observation that alcoholics respond to emotionally-valenced stimuli in an undifferentiated manner is consistent with clinical evidence of their interpersonal difficulties (Kornreich et al. 2002), and may contribute to adverse societal repercussions for alcoholics. Moreover, that both the amygdala and hippocampus were hyporesponsive is not surprising, since encoding of emotional memories depends on the hippocampus in conjunction with the amygdala, as well as their interaction (LaBar and Cabeza 2006; Phelps 2004; Richardson et al. 2004).

Less is known about the dose-response mechanism, though it has been suggested moderate drinking lies somewhere intermediate [52,53]. This would again imply that the impact of alcohol consumption on brain structure is not limited to heavy alcohol consumption. However, it has been noted there are differences in brain structure that predate alcohol initiation and may predispose individuals to heavy alcohol use. Structural precursors have mostly been found in the prefrontal cortex and fronto-limbic white matter and show considerable overlap with structural differences found in individuals with a family history of alcohol dependence [54]. Nevertheless, there are studies that have suggested differences are not solely attributable to familial risk [55,56], and more research is needed to better understand these risk factors.

When techniques are combined, it will be possible to identify the pattern, timing, and distribution of the brain regions and behaviors most affected by alcohol use and abuse. Electromagnetic methods (ERP and MEG) specify the timing of alcohol-induced abnormalities, but the underlying neural substrate (i.e., the anatomical distribution of the participating brain areas) cannot be unequivocally evaluated based on these methods alone. Conversely, the hemodynamic methods (fMRI, PET, and SPECT) have good spatial resolution but offer little information about the sequence of events.

On the other hand, the FA decrease in the thalamus first noted on day 12 persisted through day 87 (Dror et al. 2010). This model was also used in a pharmacological DTI study in which animals were exposed to rasagiline, a selective monamine oxidase B inhibitor, as a potential protective agent against thiamine-deficiency–induced brain damage (Dror et al. 2014). In addition to reducing ventricular enlargement, rasagiline appeared to ameliorate the effects of thiamine deficiency on the FA decrease in the thalamus (Dror et al. 2014). Histopathology showed that treatment with rasagiline reduced the lesions in thalamus and colliculi observed in the thiamine-deficient brain (Eliash et al. 2009).

In the current study, scientists investigate the toxic effects of alcohol on both undifferentiated and differentiated human neuroblastoma cells, the most widely used cellular model to study neurodegenerative diseases. To this end, neuroblastoma cells were exposed to millimolar (mM) ethanol for up to after the high the dea 24 hours. Trauma can lead individuals to use substances as a coping mechanism, self-medicating to relieve distressing emotions and memories. Owraghi says trauma can lead to neurobiological changes, impacting areas of the brain involved in reward processing, impulse control, and emotional regulation.

Recently, a genome-wide transcriptional assessment of human striatum found that G protein coupled receptors, the primary targets of many neurotransmitters and neuromodulators, were the top canonical pathway affected in striatum of AUD patients [70]. Reverse translation of these findings into a rodent model demonstrated putative therapeutic potential for a positive allosteric modulator of the muscarinic M4 receptor which, when delivered systemically in rats, reduced a wide range of alcohol self-administration behaviors [70]. Later controlled studies generated objective evidence what is a substance abuse counselor for an age–alcoholism interaction, in which older alcoholics had more enlarged ventricles than would be expected for their age (Jernigan et al. 1982; Pfefferbaum et al. 1986, 1988). With the advent of computed tomography (CT), significant progress was made in indexing the severity of brain shrinkage in terms of enlargement of the ventricles and regional cortical sulci (see figure 2B and C). The expansion of the fluid-filled spaces of the brain was interpreted as a sign of local tissue shrinkage rather than as irreversible tissue loss (i.e., atrophy) (Ron et al. 1982).

  1. For the purpose of this review, because numerous studies of alcoholics have reported abnormalities in the amygdala, hippocampus, and hypothalamus, the discussion is focused on those brain regions.
  2. Alcohol abuse and alcohol dependence are responsible for failure in everyday life roles and high costs to society for disability and health expenditures (APA 1994; NIAAA 1997).
  3. Over time, excessive alcohol consumption can damage both the brain and liver, causing lasting damage.
  4. However, the activation was described as only partial due to the lack of alteration alcohol had on levels of MHC-II or TNF-α expression.

Patients with Korsakoff’s syndrome are permanently unable to remember new information for more than a few seconds. Because new events are forgotten a few seconds after they occur, virtually nothing new is learned, and patients with Korsakoff’s syndrome live perpetually in the past. However, in contrast to patients with alcoholic dementia, who have generalized cognitive decline (including widespread memory loss), patients with Korsakoff’s syndrome retain old memories formed prior to the onset of alcohol-related brain damage.

Postmortem brains undergo standardized preservation procedures, enabling studies, for example, of neurochemical and genetic markers of alcoholism, by researchers throughout the world. Heavy drinking alters nerve cells and makes them smaller than normal, which can have severe, lasting effects on your brain. The impaired judgment you have when drinking alcohol may cause you to think that you can still drive, regardless of your BAC. Drivers with a BAC of 0.08 or more are 11 times more likely to be killed in a single-vehicle crash than non-drinking drivers. Some states have higher penalties for people who drive with high BAC (0.15 to 0.20 or above) due to the increased risk of fatal accidents.

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