Study finds altered brain responses to anticipated threat in individuals with alcohol use disorder

A study comparing individuals with alcohol use disorder and healthy participants found that individuals with alcohol use disorder exhibit increased connectivity between the right anteromedial thalamus and the right anterior insula regions of the brain when anticipating an unpredictable threat. These regions play critical roles in detecting internal and external signals and generating emotional responses to prepare for future events. The research was published in Biological Psychiatry: CNNI.

Alcohol use disorder is a condition in which a person struggles to control their alcohol consumption, continuing to drink despite harm to their health, relationships, or responsibilities. People with this disorder experience intense cravings and a strong psychological dependence on alcohol, often using it as a way to cope with stress or negative emotions. Over time, drinking begins to dominate their lives, reducing interest in other activities and straining social and family connections. People with alcohol use disorder may gradually develop a higher tolerance for alcohol, requiring more to feel its effects, and they often experience withdrawal symptoms like anxiety or irritability when they stop drinking.

Biologically, the chronic excessive intake of alcohol that characterizes alcohol use disorder can lead to serious health problems, including liver damage (such as cirrhosis), heart disease, and a weakened immune system. It also increases the risk of developing mental health conditions like depression and anxiety, as well as chronic illnesses like high blood pressure and certain cancers. Long-term heavy drinking can result in malnutrition, nerve damage, and cognitive impairments.

Study author Milena Radoman and her colleagues note that heightened reactivity to uncertain stressors or threats may be an important individual difference factor that drives excessive drinking as a means of avoidance-based coping. Neuroimaging studies on unpredictable stress processing have linked these processes to activity in the anterior insula, anteromedial thalamus, and dorsal anterior cingulate cortex regions of the brain.

The authors of the study sought to examine whether the activity of these brain regions differs between individuals with alcohol use disorder and healthy individuals in situations involving unpredictable threats. In doing so, they aimed to test whether heightened reactivity to threats is a specific characteristic of individuals prone to excessive alcohol consumption.

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The study included 43 adults with alcohol use disorder, aged 21 to 30 years, and 26 healthy participants. This age range was selected because epidemiological data indicate that the prevalence of alcohol use disorder increases during this period of life.

Participants underwent functional magnetic resonance imaging (fMRI) of their brains while completing a threat task. Each participant had two shock electrodes placed on their left foot, and the study authors ran tests to identify the level of shock participants found “highly annoying but not painful.” Next, the authors conducted three types of trials while recording participants’ neural activity. Each trial involved a countdown ranging from 3 to 8 seconds (with an average of 5 seconds).

In one trial, participants received an electric shock at a specific point in the countdown (at 1 second). In another trial, there was no shock. In the third type of trial, participants received an electric shock at random intervals, regardless of the countdown. This last trial created a situation of unpredictable threat, as participants could not predict when or whether they would receive a shock. A text on the screen informed participants of the type of trial they were experiencing.

Results indicated increased neural signaling from the anteromedial thalamus to the right anterior insula region of the brain in participants with alcohol use disorder during the trials in which electric shocks were unpredictable (i.e., delivered randomly regardless of the countdown). The intensity of this activity was stronger in individuals with higher alcohol intake. There were no differences between the groups in neural activity during trials in which electric shocks were predictable.

“To our knowledge, this was the first study of effective connectivity during the NPU [non-predictable-unpredictable] task in AUD [alcohol use disorder]. Because of that, it warrants replication before additional conclusions can be drawn. Designing longitudinal studies to improve our understanding of whether the observed bottom-up thalamic-insular projection was a premorbid risk factor for AUD [alcohol use disorder], an effect of cumulative alcohol exposure, or both is particularly important,”  study authors concluded.

The study sheds light on the specific neural activity patterns of individuals with alcohol use disorder. However, the design of the study does not allow for causal inferences to be drawn from the results.

The paper, “Altered Effective Connectivity During Threat Anticipation in Individuals With Alcohol Use Disorder,” was authored by Milena Radoman, K. Luan Phan, Olusola A. Ajilore, and Stephanie M. Gorka.