The study found that although adolescent and adult animals experienced seizures of various severities at a similar rate, the more severe seizures lasted significantly longer in the adult animals than in the adolescent animals. Thus, this study supports the hypothesis that adolescent animals are less sensitive than adults to alcohol’s effects on the GABA system. One brain region where particularly extensive remodeling occurs is the frontal region of the outer layer of the brain—the prefrontal cortex—which is thought to be involved in working memory, voluntary motor behavior, impulse control, rule learning, spatial learning, planning, and decisionmaking (see Spear 2000; White and Swartzwelder 2005).
In cirrhosis, elevated blood level of ammonia is thought to result in elevated brain ammonia, which can be toxic (Weissenborn et al. 2007). It often has been proposed that the brain’s response to elevated ammonia levels is to combine ammonia and glutamate to make glutamine using glutamine synthetase, found primarily in astrocytes (Yamamoto et al. 1987). The decrease in mI is thought to be a compensatory mechanism to counterbalance the osmotic effect of cerebral glutamine accumulation (Balata et al. 2003; Mardini et al. 2011). A single study measured GABA levels in five alcoholics without HE and five study participants with both alcohol and non–alcohol-related HE. Levels of mI and Cho are lowest and Glx highest in patients with HE (Geissler et al. 1997; Lee et al. 1999; Poveda et al. 2010; Ross et al. 1994; Tarasow et al. 2003). Midsagittal view of the brain, showing smaller volume of the anterior superior vermis of the cerebellum in an alcoholic man (bottom) compared with an age-matched control man (top).
Systolic (SBP) and diastolic blood pressure (DBP) were measured twice at rest, with participants in a seated position. Participants were considered hypertensive if they had SBP ≥140 mmHg, DBP≥90 mmHg, used anti-hypertensive medications, or reported diagnosis of hypertension from a physician. Number of co-morbidities was determined by a count of self-report of doctor diagnosis of heart attack, congestive heart failure, angina, arterial fibrillation, transient ischemic attack, obstructive pulmonary disease, asthma, liver disease, kidney disease, thyroid disorders, osteoporosis. As previously described 34, we used SPM12 to segment and normalize the T1-weighted MRI scans prior to using the Rnifti package in R to create vectors with mutually exclusive grey matter, white matter and cerebrospinal fluid tissue compartments. We then used the R Kernlab package to quantify the 435 variables found by Cole to best predict chronological age, and obtained the predicted age score. We calculated brain-predicted age using structural MRIs processed with the BrainAgeR program, and calculated the difference between brain-predicted age and chronological age (brain-predicted age difference, or brain-PAD).
The amygdala is partially controlled by the brain’s dopamine system (Delaveau et al. 2005), as an essential part of the brain-reward circuitry—the same system that responds to alcohol and produces feelings of pleasure when good things happen (Koob 2003). In a recent study using fMRI in our laboratory (Marinkovic et al. 2007), we observed clear evidence of differences between abstinent long-term alcoholics and nonalcoholic controls in amygdala activation to emotional materials. Faces with negative and positive emotional expressions evoked significantly stronger bilateral amygdala activity in the controls than in the alcoholics, whose activations were blunted. alcohols effects on the brain: neuroimaging results in humans and animal models pmc A similar lack of emotional differentiation to facial expressions by alcoholics also was observed in the hippocampus.
Alcohol-Induced Neuronal Damage and Impaired Neural Stem Cell Function
- Not only does this integration offer a natural extension of animal models, but it also creates the opportunity to link basic science with clinical applications.
- However, adding alcohol to the fluid after the patterned stimulation had no effect on LTP, which is consistent with the observation that alcohol consumption does not impair recall of previously established memories.
- The combination of reduced sensitivity to alcohol’s motor-impairing and sedative effects on the one hand and increased sensitivity to alcohol’s memory-impairing effects on the other hand could be particularly harmful to adolescents.
- The PET ligand 11Craclopride (RAC) is a DA D2/D3 antagonist that is useful for determining D2/D3 receptor availability (a.k.a., binding potential BP) in the striatum.
- The treatment of NSCs with alcohol decreased phosphorylation of ERK, whereas the expression of total-ERK was not affected.
Further analyses related these biological abnormalities to greater neurocognitive deficits in sALC than nsALC (Durazzo et al., 2008, 2010). Interestingly, the significant smoking-related differences in ALC were not mediated by alcohol drinking history or medical/psychiatric comorbidities; this suggests that deficits in BRS of sALC are premorbid or that other unknown environmental factors influenced our BRS measures. In sum, the typical developmental trajectories of the neural correlates of cognition and emotion are complex and likely involve large-scale shifts in network engagement as the brain becomes more efficient with increasing age. The quality and rate of these neural changes are also undoubtedly influenced by a number of individual factors such as sex, puberty, genetics, environment (including social influences), and culture (Blakemore, 2012; Crone & Dahl, 2012).
MRS Findings in Uncomplicated Alcoholism
This technique can be used to depict selective commissures (e.g., corpus callosum), projection fibers, and association fibers. A number of sources provide extensive descriptions of the principles of DTI (Basser and Jones 2002; Chien et al. 1990; Gerig et al. 2005; Jones 2005; LeBihan 2001, 2003; Pierpaoli et al. 1996; Poupon et al. 1999; Sullivan and Pfefferbaum 2011). Briefly, DTI takes advantage of the fact that MR images of the brain are predominantly maps of water protons with contrast created by their immediate environment and their motility.
- Further, the gastrointestinal tract’s ability to absorb necessary quantities of thiamine is diminished in alcoholics (Hoyumpa 1980; Thomson 2000), and the liver, which houses a large part of the body’s supplies of thiamine, may not be able to store thiamine in the same capacity if it is in a diseased state (Butterworth 2009; Levy et al. 2002).
- This mechanism likely plays a key role in situations requiring inhibition of over-learned behavior, such as abstaining from alcohol.
- Brain development continues during adolescence, which could render the adolescent brain particularly vulnerable to alcohol’s effects.
- In addition, alcohol particularly affects the ability to form explicit memories—that is, memories of facts (e.g., names and phone numbers) or events (e.g., what the drinker did the previous night).
While at follow-up the size of prefrontal lobes remained unchanged, volumes of the lateral ventricles decreased (5-6% reduction) in alcohol patients with abstinence and improved drinking behavior, especially in patients that underwent only one detoxification. The extent of the ventricular enlargement correlated with the elevation of alcohol related laboratory measures (mean corpuscular volume, gamma-glutamyl transpeptidase). In conclusion this study confirms the hypothesis that alcoholism causes brain damages that are partially reversible. It should be analyzed in further studies with larger sample sizes, if complete brain regeneration is possible maintaining abstinence over a longer period. Co-use of multiple substances may also influence the relationship between neural correlates of spatial working memory and alcohol use. Given the high rates of co-morbid alcohol and other substance use during adolescence (Terry-McElrath & Patrick, 2018), future well-powered studies would benefit from a more detailed analysis of various combinations of addictive substances on neurocognitive outcomes.
Data availability
This mechanism likely plays a key role in situations requiring inhibition of over-learned behavior, such as abstaining from alcohol. Overall performance was similar in abstinent alcoholics and controls; however, alcoholics showed attenuated benefits from repetition of validly cued congruent Stroop trials. This can be interpreted as compromised implicit learning for repetitive, more automatic stimulus–response mappings. The behavioral results were reflected in brain activity showing similar lateral frontoparietal activity during Stroop task processing in both groups, but a failure in alcoholics, in contrast to controls, to deactivate the PCC. Deactivation of the PCC, a key node in the DMN, during task processing is a normal pattern and was related to higher fractional anisotropy (FA), that is, integrity, of posterior cingulum fibers in controls. Furthermore, PCC and midbrain activities were modulated by task demands in controls showing deactivated PCC and midbrain during more automatic, repetitive task conditions and activated PCC and midbrain during more effortful, switching conditions.
Major Changes in Brain Structure and Function During Adolescence
In vivo imaging techniques, by allowing for longitudinal observations of alcoholism throughout the course of the disease can unravel disease processes and may potentially contribute to the development of improved medications. Although in vivo MRS studies in both humans and animals have persisted in interpreting elevations in brain Gln as reflecting elevations in peripheral ammonia and brain edema (Venkatasubramanian et al. 2001), ex vivo carbon 13 nuclear MR studies have challenged the convention that glutamine accumulation is the major cause of brain edema in acute HE. Such studies instead indicate limited metabolic pathway reactions and capacity of astrocytes to detoxify ammonia by glutamine synthesis and emphasize distortions of energy and neurotransmitter metabolism (Zwingmann 2007). In monkeys trained to voluntarily consume alcohol, those that drank at least 3 g/kg EtOH per day for 15 months showed significant brain-volume shrinkage in the cerebral cortices (Kroenke et al. 2014).
However, alcohol misuse among adults often involves more regular drinking patterns, which may be better represented by more continuous exposure models. Taken together, these studies tend to show both pre-existing and alcohol-induced aberrations of neural correlates of cue-reactivity in adolescents. Greater alcohol use appears to result in enhanced BOLD response to alcohol cues, particularly in frontal and cingulate regions. Importantly, the effects of alcohol on alcohol cue-reactivity seem to abate to control levels following prolonged (28-day) abstinence in youth (Brumback et al., 2015), suggesting that the neural alterations induced by alcohol are highly malleable, at least during the period of adolescence. Abnormalities in DLPFC and ACC have been related to deficits in executive skills; abnormalities in the same regions and OFC, insula, superior corona radiata and ventral striatum have been related to greater impulsivity as well as impaired stimulus-reinforcement association learning (particularly OFC). Changes in many of these regions plus the amygdala and hippocampus are implicated in mood and anxiety disorders that are often comorbid with alcohol dependence and have been shown to be critically involved in the relapse/remit cycle.
Animal studies have shown that repeated exposure to alcohol during adolescence, especially AIE that mirrors binge-drinking patterns observed in human adolescents, induces specific patterns of sustained neurobehavioral alterations that may promote further drinking. Particularly worrisome are reports that adolescent alcohol exposure may lead to the retention of adolescent phenotypes—including adolescent-typical responses to alcohol—into adulthood. Other cognitive, behavioral, and affective consequences have been reported after AIE, including impaired performance of executive functions, memory impairment, reduced cognitive flexibility, greater risk preference and disinhibition, and elevated social (and sometimes general) anxiety. In many cases these effects are specific to adolescent alcohol exposure and are not evident after equivalent alcohol exposure during adulthood.
New connections among neurons are being formed; at the same time, a substantial number of existing connections are lost (see Spear 2000). It is hypothesized that this plasticity allows the individual’s brain to be sculpted based on his or her personal experiences and interactions with the outside world (Chugani 1998). Because the taste of alcohol is aversive to most animals, heterogeneous stock rats for example, consume only modest amounts of ethanol and blood alcohol levels (BALs) achieved are minimal. One of the criteria for a successful animal model of alcoholism is the demonstration of physical dependence per se must be unequivocally attributed to the chronic administration and subsequent removal of ethanol. Common models to induce physical dependence to alcohol (cf., Mello, 1973) include exposure to ethanol via drinking (e.g., Xu et al., 2018), intraperitoneal (i.p.) (e.g., Liew et al., 2016) or intragastric (i.g.) (e.g., Luo, Shen, Chen, Wang, & Yu, 2017; Zahr, Rohlfing, et al., 2016) injections, and vapor chambers (e.g., Frischknecht et al., 2017).