In sum, cross-sectional studies of adolescent drinkers consistently observe altered neural correlates of spatial working memory; however, severity of alcohol use, sex, and co-use of other substances appear to be important moderating factors that complicate the relationship. Furthermore, prospective longitudinal studies on this domain of cognitive functioning are needed to determine whether the neural differences observed function as a risk factor, or represent a consequence of alcohol use. Resting state fMRI studies, which are devoid of any task demands, generally suggest that interactions between functional brain networks reduce with age, possibly reflecting increased efficiency in between-network communication and increased within-network communication (Blakemore, 2012).
Parsons (1994) reported that although alcoholic men and women showed impaired performance on neuropsychological tests relative to same-sex nonalcoholic control participants, only the alcoholic men differed from their controls on a measure of visually evoked event-related brain potentials. Other investigators found that alcoholic men and women displayed similar electrophysiological abnormalities (Hill and Steinhauer 1993). After correction for multiple comparisons, the cerebellar cortex and somatosensory cortex each approached having a significant age × sex × treatment × time interaction. Interestingly, adult males showed alcohol effects on both of these regions despite showing no overall effects on whole brain volume.
Participants
- Detailed images of the brain are possible in part because the different brain tissue types (i.e., gray matter, white matter, and cerebrospinal fluid CSF) contain different proportions of water (Rumboldt et al. 2010).
- This hyperexcitability can be analyzed not only through behavioral measures, such as convulsions, but also through electrophysiological changes in brain activity.
- In addition to these two neurotransmitter systems, a system using the neurotransmitter glutamate also appears to undergo changes during adolescence.
- In laboratory animals, sedation can be assessed by observing the righting reflex that normally helps the animals get back on all four feet if they fall over.
Studies included neuropsychological testing, visual and short-latency auditory evoked potentials, and morphometric analysis of computed tomography scans. Compared to control subjects, chronic alcoholics exhibited a significant prolongation of the PI00 latency of visual evoked potentials, and a prolongation and reduction in the amplitude of the latency of the V wave of short-latency auditory evoked potentials. Brain morphometric analysis showed that alcoholics had a significantly greater degree of brain shrinkage with age, compared to control subjects. Neuropsychological testing in alcoholics compared to controls revealed a significant impairment of frontal skills that was related to age, degree of scholarship, and the presence of frontal atrophy. In conclusion, well-nourished chronic alcoholics exhibited significant brain impairment, as demonstrated by neuropsychological testing, evoked potentials, and brain morphometric analysis, which was correlated with the lifetime dose of ethanol consumed.
- A single study measured GABA levels in five alcoholics without HE and five study participants with both alcohol and non–alcohol-related HE.
- Preclinical imaging has the potential to provide greater understanding of the dynamics of alcohol-related effects on the structure, metabolism, and function of the brain.
- Moreover, increased μ-opioid receptor availability in the ventral striatum of detoxified alcoholics correlates with self-reports of craving intensity (Heinz et al., 2005).
- Perhaps the most consistent evidence of greater RH dysfunction has come from studies utilizing electrophysiological measures, although this observation has to be tempered by the poor spatial resolution of ERPs.
- 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).
- While this limits confounding due to differences in these measures, results may not generalize to other populations.
Alcohol-induced disinhibition is reflected in premature motor preparation based on incomplete stimulus evaluation as measured by event-related potentials (ERPs; Marinkovic et al. 2000). Furthermore, these disinhibitory effects of alcohol are correlated with personality traits related to impulsivity and hyperactivity (Dougherty et al. 2000; Marinkovic et al. 2000). Recent models of vulnerability to alcoholism emphasize the importance of executive functions in mediating, as well as moderating the effects of alcohol (Finn 2002; Giancola 2004). Over the past 40 years, rigorous examination of brain function, structure, and attending factors through multidisciplinary research has helped identify the substrates of alcohol-related damage in the brain. One main area of this research has focused on the neuropsychological sequelae of alcoholism, which has resulted in the description of a pattern of sparing and impairment that provided an essential understanding of the functional deficits as well as of spared capabilities that could be useful alcohols effects on the brain: neuroimaging results in humans and animal models pmc in recovery. These studies have elucidated the component processes of memory, problem solving, and cognitive control, as well as visuospatial, and motor processes and their interactions with cognitive control processes.
Before each training session, one group of animals received no alcohol, and two other groups received one of two different alcohol doses. The investigators then compared how long it took the alcohol-exposed and control animals to remember the location of the platform. Among the adult animals, only those exposed to the highest alcohol concentration showed learning impairments compared with the control group. In contrast, adolescent animals also showed impairments after they had received the lower alcohol dose (Markwiese et al. 1998). This experiment demonstrates that adolescent rats are more vulnerable to alcohol’s effects on memory and learning than are adult rats.
For practical, evidence-based tips on supporting your patients with AUD, see the Core articles on treatment, referral, and recovery. During acute and protracted withdrawal, a profound negative emotional state evolves, termed hyperkatifeia (hyper-kuh-TEE-fee-uh). In addition, effects can differ depending on the time lapsed since ingestion; the same BAC may result in different effects on the ascending versus descending limbs of the BAC curve (Pohorecky and Brick 1977).
NICOTINE DEPENDENCE AND ITS POTENTIAL IMPACT IN CLINICAL TREATMENT
Hepatic Encephalopathy (HE) is believed to arise from high levels of ammonia circulating in the blood stream, occurring during acute or chronic liver disease, often as a consequence of alcoholism. Altered ammonia levels in the body directly influence brain metabolism and can lead to glial swelling and neuronal cell death (Kundra, Jain, Banga, Bajaj, & Kar, 2005; Rama Rao & Norenberg, 2014). HE patients may appear confused, disoriented, and have poor coordination (Prakash & Mullen, 2010; Vaquero, Chung, Cahill, & Blei, 2003). MRI images show bilateral, symmetrical high-intensity signals in the basal ganglia, prominent in globus pallidus, and substantia nigra (Figure 1C) (Binesh et al., 2006; Cordoba, Sanpedro, Alonso, & Rovira, 2002; Naegele et al., 2000), as well as along the cortico-spinal tract and white-matter of the cerebral hemispheres (Rovira et al., 2002). (A) Brain scan of an alcoholic man with Wernicke’s encephalopathy showing the typical hypertensities in the mammilary bodies and colliculi (reprint with permission from (Sullivan & Zahr, 2008)).
Adolescents Are More Sensitive Than Adults to Alcohol’s Memory-Impairing Effects
Another large area of research has focused on observable brain pathology, using increasingly sophisticated imaging technologies–progressing from pneumoencephalography to computed tomography, magnetic resonance imaging (MRI), diffusion tensor imaging, and functional MRI–that have enabled ever more detailed insight into brain structure and function. These advancements also have allowed analysis of the course of brain structural changes through periods of drinking, abstinence, and relapse. Because of differences between species, ages and treatment paradigms used across studies, further research will be required before broad conclusions about how EtOH affects these regions can be drawn. Rodent models of alcohol use during adolescence have illuminated possible neurobiological avenues of alcohol’s effects on cognitive functioning.
3.3. Adolescent females
These findings clearly demonstrate that, in contrast to alcohol’s effects on memory, adolescent rats appear to be less sensitive to alcohol’s effects on motor coordination than adult rats. It is clear, however, that the cerebellum, which plays a critical role in motor coordination, still is developing quite rapidly during adolescence. If the cerebellum is less sensitive to alcohol during this period, this could account for the developmental difference in sensitivity to alcohol. Each of the syndromes is characterized by extensive structural deviations from a healthy brain; the morphological changes, however, are not exclusively linked to a diagnosable neurological disorder.
Differential Effects of Acute Alcohol on Memory in Adolescents and Adults
Methods are used for acute and binge like protocols, while free drinking and vapor chambers are used for more chronic exposure protocols (Bell et al., 2017). While vapor chambers are the preferred method for sustained high BALs, in addition to inhalation, animals are exposed to ethanol via skin absorption. Problems with drinking protocols include a transitory alcohol preference in the absence of withdrawal signs and symptoms upon cessation of drinking.
3. Whole brain volume
Investigators in the alcohol field have begun to emphasize the integration of neuroimaging and genetic approaches (e.g., Boettiger et al., 2007; Heinz et al., 2007; Hutchison et al., in press). This special topic section of ACER features the work of four groups who are developing translational phenotypes based on neuroimaging. Bragulat et al. present a unique approach that involves the combination of intravenous ethanol infusion and the presentation of olfactory cues in the scanner. This study represents a thoughtful approach to investigating the effects of a highly controlled priming dose of ethanol on brain activation in response to alcohol cues. A unique advantage of this approach is that the priming dose is highly controlled with the intravenous infusion, which is likely to yield a phenotype that is sensitive to genetic variation that may influence the effects of ethanol on cue-elicited brain activation.
We then investigated the molecular mechanisms that underlie the alcohol inhibition of neuronal differentiation, specifically the expression of ERK and its phosphorylated (active) form after alcohol exposure. The treatment of NSCs with alcohol decreased phosphorylation of ERK, whereas the expression of total-ERK was not affected. To confirm the involvement of ERK in the mechanism of alcohol inhibition of neuronal differentiation, we treated NSCs with U0126, a mitogen-activated ERK kinase (MEK) inhibitor. U0126 treatment of NSC reduced neuronal differentiation and decreased the generation of neurons.95 Furthermore, the effect of U0126 on the DNA binding activity of NRSF was measured by treating NSCs with various concentrations of U0126, which revealed that U0126 potentiated the NRSF binding activity at the same concentration which suppressed neurogenesis.