If I can’t remember it, it didn’t happen: A susceptibility for alcohol-induced blackouts

As anyone who’s ever taken an Alcohol Edu course (or been 21 in the last decade) knows, consuming too much alcohol can cause memory loss, colloquially known as a “blackout”. This anterograde amnesia stems from an inability of the brain to form new long-term memories and is caused by a disruption in the GABA and NMDA receptors in the prefrontal cortex (PFC) and medial temporal lobes when drinking.

First, for those of you who skipped (or drank) your way through your alcohol education, a brief reminder on the effects of alcohol on the brain. GABA is a primary inhibitory neurotransmitter, acting to decrease the likelihood of a cell’s firing. Alcohol acts as a GABA agonist, elevating levels throughout the brain and therefore diminishing the rates of firing in normal cellular processes. At high levels, alcohol also acts upon glutamate NMDA receptors, one of the main excitatory neurotransmitter systems. Alcohol works as an NMDA antagonist, blocking the NMDA receptors and preventing glutamatergic activation, further inhibiting neuronal functioning. This inhibition particularly occurs in the PFC, medial temporal cortex and the parietal lobe, primary targets of alcohol in the brain. In the hippocampus in particular, an area in the medial temporal cortex crucial to memory formation, this inhibition can result in a disruption of long-term potentiation, a cellular process involved in the consolidation of short-term to long-term memories.

Alcohol’s effect on the PFC also impacts memory ability, as short-term memories are maintained there while they are being worked on or rehearsed. However, when attention shifts to a new stimulus this memory must be consolidated into a more stable long-term version via cellular activity in the hippocampus, or else it will be discarded and forgotten. Alcohol’s inhibition of the PFC via its effects on GABA and glutamate can disrupt the maintenance of these short-term memories, decreasing the likelihood of consolidation and preservation. The dampening of firing in the PFC is also attributed to the behavioral disinhibition that so commonly succeeds alcohol consumption, as the PFC can no longer inhibit or control impulses as well.

Now, on to the exciting bit! In individuals who regularly experience alcohol-induced memory loss, or a blackout, it is the contextual memory that seems to be most impaired. This refers to the details surrounding an experience, such as where, when and with whom the event occurred. However, blackouts seem to affect some drinkers more than others, and are not necessarily determined by the amount of alcohol that an individual consumes. Simply put, you either blackout when drinking large amounts of alcohol or you do not.

Published online this week in Alcoholism: Clinical and Experimental Research, psychologists from the University of California, San Diego and the University of Texas, Austin have recently confirmed this urban drinking legend by testing 24 regular binge drinkers, 12 of whom admitted to blacking out on a regular basis, reporting on average two blackouts per month, and 12 who drank comparable amounts of alcohol but declared no memory problems when drinking. Both groups were matched on their typical alcohol consumption, averaging 3 drinking days per week and consuming 4-5 drinks at a time on a typical day when drinking. Both groups also had comparable binge tendencies, consuming 10 or more drinks on occasion over the previous 3 months.

Participants were tested on a contextual memory task using functional magnetic resonance imaging (fMRI) both when sober and after drinking to a blood alcohol content of .08, the legal limit in the United States, typically 3 drinks for a male and 2 for females. During both the sober and intoxicated trials, participants performed equally well in their behavioral scores, recalling similar amounts of information regardless of their blackout group status. Groups also did not differ in their response times on the task during either condition, however both groups recalled significantly fewer trials when intoxicated and were significantly slower than when sober.

In the imaging analysis, there were no differences in activation levels between the groups during either encoding or retrieval for the sober condition of the task. However, when intoxicated, both groups demonstrated significantly less activation in the right frontopolar PFC during retrieval. The blackout group also had significantly less activation during both the encoding and recall portions of the experiment after consuming moderate amounts of alcohol as compared to the non-blackout group. Specifically, participants with a history of blacking out showed less activation in the left frontopolar PFC during encoding, and decreased activity in the right posterior parietal cortex and the bilateral dorsolateral PFC during retrieval as compared to their non-blackout contemporaries. This fronto-parietal network is implicated in attentional maintenance and inhibition, as well as working memory and executive control, suggesting that there could be greater difficulties in these skills in the blackout group when drinking.

The researchers speculate that the decrease in activity in the frontal pole during intoxication is indicative of an alcohol-induced impairment in executive functioning in both groups, particularly in regards to working memory and cognitive maintenance. The additional decrease in activation in the fronto-parietal network seen in the blackout group also suggests a greater disability in executive functioning and memory maintenance in these individuals when drinking. However, it is notable that there were not any significant behavioral differences between the two groups in total memory recall, particularly during the intoxication condition.

While it is reassuring that there were no impairments in either group during the sober condition, the drinking results do seem to suggest that there may be underlying problems with memory and executive functioning in those individuals with a proclivity for forgetting, which could emerge after more chronic drinking behaviors. Why some people are predisposed towards these additional memory impairments is still unclear, but there does seem to be something different in the brains of those who blackout regularly that is not just dependent on the amount of alcohol they drink.

(Insert poor taste joke about drinking away your memory problems here.)

The healing power of the brain-gut connection

Anyone who’s ever tried to cure the blues with Ben and Jerry’s knows that there is a link between our stomachs and our moods. Foods high in fat or sugar release pleasure chemicals into the brain in much the same way that drugs do, and chocolate in particular is frequently touted as a mood-elevating treat. Now research from a team of pharmacologists in Ireland provides new support for this brain-gut connection, showing that probiotic bacteria, like those found in many strains of yogurt, can elevate mood and reduce anxiety.

Formally referred to as the microbiome-gut-brain axis, this system has been implicated in stress responding, with gut microflora affecting the HPA (hypothalamic-pituitary-adrenal) axis and altering stress and anxiety responses. In the current study, researchers gave mice Lactobacillus rhamnosus and then subjected them to various stress-inducing tests. Mice who had been fed the probiotic solution demonstrated less freezing or fear-response behaviors compared to those who were given plain broth. They were also more likely to explore exposed novel environments in an elevated maze, an indication of security and lack of anxiety. Finally, on a depression assessment, mice were placed in a forced swim test (also called the behavioral despair test), where they were submerged in water and had to struggle to stay afloat. Lack of effort and time not spent attempting to swim are seen as indicators of depression and hopelessness, and probiotic-fed mice had less immobility time than broth-fed mice. Corroborating these behavioral results, test mice also had lower levels of corticosterone after being stressed than control mice.

This interaction between the brain and the gut is facilitated by the vagus nerve, a cranial nerve that transmits sensory information from internal organs to the brain. When this nerve was cut the effects of the probiotics disappeared, and test mice had decreased exploratory behavior and greater periods of immobility, similar to the broth-fed mice.

The anxiolytic effects of L. rhamnosus seem to be tied to GABA, an inhibitory neurotransmitter involved in anxiety. Probiotic administration altered levels of GABA mRNA expression in regions of the brain, including the amygdala, hippocampus, and prefrontal cortex. In depressed individuals, GABA levels in the frontal cortex are shown to be reduced, but in the probiotic-fed animals, cortical GABA levels were elevated. This led the researchers to theorize that L. rhamnosus might help to protect against stressful or anxiety-producing events. GABA levels in the amygdala are also commonly elevated in depressed individuals, and GABA antagonists (which reduce the levels of the neurotransmitter in the brain) are sometimes used as antidepressants. In the current study, lower levels of GABA were found in the hippocampus and amygdala after probiotic consumption, suggesting an interaction between L. rhamnosus and the memory and emotional centers of the brain, potentially increasing associative learning and memory consolidation and decreasing fear responding to stressful events.

The connection between diet and behavior doesn’t just apply to stress. Certain highly specified restrictive diets have also been used to help treat and control a variety of neurological disorders, most notably epilepsy. First pioneered in the 1920s at John’s Hopkins Children’s Hospital, extreme high-fat/low-carbohydrate diets are gaining support as a possible alternative for drug-resistant epilepsy, though some physicians are still skeptical. The diet works by invoking ketosis, a process in which the body burns fat stores rather than carbohydrates for fuel. This typically occurs when the body is in a starvation state and is the premise on which low-carb diets are based. However, ketogenic diets also appear to have an antiepileptic effect, particularly in cases of severe pediatric epilepsy. Doctors are not sure why the treatment works, but one theory is that the ketone bodies produced by the liver when the body burns fat protect neurons from damage, though how or why this happens is still unknown.

A keystone paper from University College London published in 2008 was the first to empirically report the efficacy of the ketogenic diet, and a recent provocative profile in the New York Times of a family dealing with epilepsy, “keto,” and the trials it brings has brought this treatment to national attention. The diet itself is strictly regimented and incredibly difficult to follow. It requires exact caloric measurements and proportions of protein, carbohydrates, and fats, with roughly a 3-to-1 fat to carb/protein ratio. This relates to a diet of roughly 90% fat, which can be dangerous, potentially triggering kidney problems and malnutrition. However, the effectiveness of the treatment is gaining recognition, and patients who are on the ketogenic diet (mostly children) are carefully monitored for cholesterol levels and cardiovascular health.

The ketogenic diet is now being looked at to potentially treat other serious medical disorders, such as Parkinson’s disease and cancerous tumors. It is important to note, though, that individuals being treated with a prescribed diet are also frequently on concomitant medication. Diet alone will not be able to cure all ailments, but the connection between diet and mental and physical health cannot be denied, and in the very least it is a good place to start keeping yourself well and taking preventative action.