Multiple Detoxification Damages Brain Areas Required For Alcohol Abstinence [Research Study]

Shruti Baikerikar

(B.E. Biotechnology, PG Clinical Research)
Independent Researcher, Health Writer & Founder of Salubrainous [Full Bio]

multiple detoxification damages brain areas vital for abstinence

Treatments for addiction target the brain processes in two ways:

  • Bottom-Up: They target parts of the brain below the cortex (which is the largest area of the brain) such as the reward pathways.
  • Top-down: They enhance prefrontal cortical function (front part of the brain).

Pharmacological treatments or medicines have a bottom-up target while behavioural treatment has a top-down target.

The bottom-up target focuses on how to inhibit our desire or response to the incentive of consuming drug or alcohol while the top-down target focuses on modulating our behaviour so as to control the desire to consume drug or alcohol.

The desire to seek and consume drug and alcohol is fuelled by certain experiences where the individual has learned that consuming these agents is rewarding or provides momentary pleasure.

He feels ‘incentivised’ or motivated to continue such behaviour. Such incentive processes are mediated by brain networks such as [1]:

  • ventral striatum: part of the brain involved in our reward system
  • orbitofrontal cortex: part of the brain located above our eye sockets and involved in decision making and reward learning
  • medial prefrontal cortex: part of the brain involved in reward learning and decision making about risk and reward

Being exposed to incentives is not enough to make one consume alcohol or drugs.

One needs to override signals from other parts of the brain that are involved in higher-order functioning and tell you whether it is safe or not to consume such substances.

These parts of the brain are capable of interrupting such incentive processes and they aid in impulse control.

Such control is mediated by the interaction of two parts of the brain:

  • prefrontal cortex: involved in decision making
  • striatal output system: involved in reward learning and decision making

Alcohol abuse damages such areas of the brain that would otherwise help control the urge to drink. [2]

Alcohol has long-term damaging effects on the prefrontal cortex structure and function. [3]

Scientific studies suggest that these effects get worsened with multiple detoxifications in comparison to single detoxifications [4]

Repeated experience of alcohol withdrawal disturbs the cognitive function of patients with alcohol addiction.

Therefore, Duka and colleagues hypothesized that patients with alcohol addiction would show a deficit in performance on a cognitive task which would measure their impulse control or abstinence.

Also, they predicted that those who had undergone multiple detoxifications would perform worse.

Further, they decided to conduct a neuroimaging (brain scan) study to understand which parts of the brain are activated when a healthy individual performs optimally in such tests and whether these parts are structurally damaged in patients with alcoholism.

This study was conducted by researchers from the University of Sussex (UK), King’s College (UK), Monash University (Australia) and Sussex Partnership NHS Foundation Trust, Brighton, United Kingdom.

How was the study conducted?

45 individuals participated in the cognitive task. 23 were diagnosed for alcohol dependence and 22 were healthy social drinkers.

60 individuals, 29 alcohol dependent and 31 social drinkers, participated in the neuroimaging study that examined structural changes in the brain.

14 healthy individuals participated in the neuroimaging study that identified which brain areas were activated while performing the cognitive task.

All patients with alcoholism remained abstinent for a minimum of 2 weeks prior to the study and did not use any psychotropic medication prescribed for detoxification for 72 hours before the testing.

Incentive Conflict Task

The cognitive task used here was an incentive conflict task. Researchers used this task to understand the ability of a person to abstain from responding to incentive cues.

First, a training phase was conducted so as to proceed only with individuals who showed awareness.

incentive conflic task

Image Credit: Taken from Supplementary Data, Duka, Theodora et al. “Unique Brain Areas Associated with Abstinence Control Are Damaged in Multiply Detoxified Alcoholics.” Biological Psychiatry 70.6 (2011): 545–552.

The tests were conducted in the following ways:

Incentive Conflict For Patients With Alcohol Addiction

There were shown two pictures labelled A and B. Then they were asked how likely they are to get a reward.

The response to this question involved rating: 1=likely and 9 unlikely.

After that, they would have to press the spacebar to get the result.

Picture A alone (A+) led to a reward of 10 pence and Picture B (alone, B+) also gave the same reward. But if both pictures A and B were shown on the screen it meant a loss of 10 pence (AB-).

Pressing spacebar after seeing both picture A and picture B on the screen (AB-) meant a loss of 10 pence.

These images were shown at random to the participants.  Participants were labelled as ‘aware’ if their expectancy ratings for A+ and B+ was greater than 5.

The purpose of this experiment was to identify whether patients could understand which images were associated with a reward and which images were not.

And also, could they control the urge to press the spacebar when they were shown an image that did not give a reward.

Incentive Conflict & Neuroimaging (fMRI) For Healthy Individuals

In this incentive conflict test, apart from stimuli, A and B researchers introduced new stimuli to develop a comparison.

They were:

  • C- : image C means a loss of reward
  • D- : image D means a loss of reward
  • CD- : both images C and D shown simultaneously means a loss of reward

Participants were shown images A+, B+, AB-, C-, D- or CD-. A neuroimaging study was also conducted to understand which brain areas were activated.

This helped researchers compare and understand specific brain responses to the multiple stimuli.

Further, a reverse test was conducted where A+ was changed to A-. In this test, presentation of image A meant a loss of reward.

So A- was mixed with images B+, C-, D- to control the reversal of reward.

Neuroimaging was conducted during these tests and the data was collected and compared to understand which parts of the healthy brain are activated when performing such tests.

Structural MRI For Patients

Finally, a neuroimaging study (structural MRI) was conducted in patients with alcohol addiction. This helped to evaluate any changes in five parts of the brain of patients with alcoholism:

  • putamen
  • ventromedial prefrontal cortex
  • gyrus rectus
  • superior frontal gyrus
  • supplementary motor area

These parts of the brain are associated with the performance in the incentive conflict task.

Statistical analysis of the data was conducted.

What were the results of the study?

During the training phase, 12 out of 23 patients and 15 out of 22 healthy individuals became aware of the predictive nature of the images A+ and B+.

Researchers proceeded with the incentive conflict stage only with those who showed awareness.

Results of Incentive Conflict Test: Patients vs. Healthy Social Drinkers

In the incentive conflict task, when exposed to AB- stimulus patients with alcoholism gave incorrect higher reward expectancies than the control group (healthy social drinkers).

Both groups gave higher reward expectancy ratings for A+ and B+ than AB-, and this was indicative of awareness.

Individuals in the control group had higher anxiety ratings for AB-  when compared with A+ and B+ while patients with alcohol addiction showed similar ratings for all stimuli.

Results of Incentive Conflict Tests: Multiple Detoxification vs. Single Detoxification

Among the patients with alcoholism, 8 patients had 2 or more detoxifications while 15 had one or no detoxifications before the current one.

For images A+ and B+, both groups had equal reward expectancy ratings of around 8.02.

However, when presented with AB-, patients with multiple detoxifications had highest reward expectancy ratings and probability of reward (they incorrectly anticipated reward) followed by single detoxification patients followed by the control group.

This indicated that multiple exposures to detoxifications affected the performance on cognitive tasks that measured abstinence and impulse control.

Neuroimaging Of Incentive Conflict For Healthy Individuals

Brain scan images of healthy individuals revealed the brain responses to incentive conflict task.

The three aspects of the task activated different parts of the rostral frontal cortex:

  • Test phase: medial orbitofrontal cortex was activated
  • Incentive Conflict phase: ventromedial prefrontal cortex, gyrus rectus and superior frontal gyrus was activated
  • Reversal phase: the lateral orbitofrontal cortex was activated

Neuroimaging (Structural MRI) of Patients With Alcohol Addiction

Brain scans revealed that patients with alcoholism had reduced grey matter volume compared to healthy social drinkers and this was more pronounced in patients who had undergone multiple detoxifications.

Reductions were observed specifically in parts of the brain that were involved in incentive conflict tests such as ventromedial prefrontal cortex and superior frontal gyrus.

More the number of detoxifications, greater was the reduction. Detoxification selectively damaged subset of prefrontal areas of the brain (front part of the brain).

What is the significance of the results?

The study results demonstrated that patients with alcoholism are severely impaired in performing a cognitive task that evaluates their impulse control and abstinence.

Multiple detoxifications worsened their performance even more. Patients who had two or more detoxifications performed worse than those who had had a single detoxification.

Higher the number of detoxifications greater was the deficit in both brain structure and function.

Studies in animal model indicate that repeated episodes of alcohol withdrawal impair behavioural and cognitive function. [5]

However, the researchers do acknowledge the possibility that the impaired performance on the cognitive task could be due to a pre-existing condition which drove them to alcoholism in the first place or increased the tendency to undertake detoxification.

They highlight genetic polymorphism (multiple forms of a gene) in the DRD2 gene is associated with alcoholism severity and increase in number of attempts of detoxification. [6]

To understand the brain activity during incentive conflict task, researchers conducted a brain scan only of healthy individuals.

Since the performance of alcohol addiction patients was so severely impaired, they anticipated that they would not receive sufficient data if they conducted neuroimaging for them.

The parts of the brain that were activated during the task had the following functions:

  • Cognitive and emotional processing (dorsal striatum, subregions of the orbitofrontal and ventromedial cortex, supplementary motor area) [7]
  • Self-regulation and behavioural control (superior frontal gyrus) [8]
  • Emotional regulation, especially the feeling of regret caused by loss of reward (gyrus rectus) [9] [10]

While several parts of the brain were activated during the incentive conflict task, structural damage to the brain in patients with alcohol addiction was limited to a subset of these regions.

In particular, the ventromedial prefrontal cortex and superior frontal gyrus were damaged. These are involved in motivational decision making and behavioural control. [11] [12]

These cognitive processes are vital for alcohol abstinence. These deficits reflect an inability to learn to avoid negative outcomes and such deficits hold relevance even in daily life.

The study had limitations. No imaging was conducted during incentive conflict task for alcoholism patients.

So the researchers can’t be sure where the impaired performance was a result of reduced brain activation and function or was their performance impaired despite the activation.

Also, no data was recorded on patient’s responses to single stimuli that predicted lack of reward (C-, D-).  This would have helped understand whether the patients had a general deficit in learning under confusion.

Conclusion

In their study, Duka et al. observed that patients with alcohol addiction have structural and functional deficits in the prefrontal cortex occurring as a direct consequence of alcohol use and withdrawal.

Multiple detoxifications make the patient susceptible to such damage.

This, in turn, may impair their performance on incentive conflict resolution (choosing between risk and reward) and thus may impair their control or ability to abstain from alcohol leading to relapse.

Read Full Research Paper at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165202/

Reference:

Duka, Theodora et al. “Unique Brain Areas Associated with Abstinence Control Are Damaged in Multiply Detoxified Alcoholics.” Biological Psychiatry 70.6 (2011): 545–552. PMC. Web. 4 Aug. 2018.

Research shows that multiple detoxifications can damage brain areas in alcoholism patients that are vital for alcohol abstinence.

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