Substance Use and the Brain: How Substance Use Affects Thinking

Susan F. Tapert, Ph.D.

4/5/05

I. Overview.

A. How substance use affects brain functioning. In this 20-minute lecture, we will discuss how heavy, chronic use of substances affects brain functioning and health. We will focus on the 3 most commonly misused substances:

1. Alcohol

2. Marijuana

3. Stimulants

B. Recovery with long-term abstinence. We will also discuss how these problems can remit with sustained abstinence.

II. How is the brain affected? (long-term) I’ll spend most of the time on alcohol, and then briefly discuss other drugs. We will focus on persisting effects only.

A. Alcohol

1. Thinking abilities (time course of recovery)

a. Researchers have been studying thinking abilities in alcoholic individuals for decades, and consistently find problems in certain areas. These results are based on lots of tests looking at different areas of thinking abilities. Alcohol-dependent adults show thinking deficits in certain areas:

i. Learning and memory—takes more trials to learn something, and it’s hard to remember things (grocery lists); may make it hard to remember what happened in a day, or what was learned in treatment

ii. Planning - coming up with a strategy when presented with a new problem

iii. Making good decisions

iv. Spatial skills, like reading a map or following directions to a place

v. Motor skills

vi. hand-eye coordination—ability to do well in sports

vii. Fine, detailed movement

b. Recovery—thinking skills will improve with sobriety. Patients who remain sober for several months or more always tell us how their memories have improved.

2. Sleep

a. When drinking, alcohol suppresses REM sleep

b. Early in recovery, it’s hard to fall asleep, and you have increased REM sleep so folks often don’t feel rested. This can be a risk for relapse.

3. Brain structure

a. As the saying goes, “If you drink, your brain will shrink”. Here are some MRI images we collected at the San Diego VA. These images are a top view, taken from about ear-level. There is a lot more black spaces in the brain of the guy with alcoholism.

b. The brain images are a side view. All the black parts are fluid-filled spaces. Everyone has them, and as we age, they get larger because the brain starts to shrink, so the fluid filled spaces get larger. The image on the left is a guy we recruited from the ADTP. The image on the right is a healthy control, about 40 years old. He’s a guy about the same age without an alcohol problem. You can see that the guy on the right has a lot more black spaces. This is evidence that his brain has shrunk. This guy is only about 40 years old.

c. Also, this part down here (POINT) is called the cerebellum. It’s involved in coordination and movement. So you know how if you have to do the roadside sobriety test, it’s really hard. This is because alcohol really affects how this part functions. After years of alcoholism, this part gets damaged. You can see from these images, that the man with alcoholism has a much smaller cerebellum. This is related to age too. Younger brains are more resilient to alcohol’s effects. But as you get older, your brain is less able to cope with the damage. Also, the part of the brain involved in learning is smaller in alcoholic individuals. This may be related to why alcoholics have a hard time learning and remembering. This part seems to be particularly affected by the severity of withdrawal symptoms. Guys who experienced withdrawal seizures had smaller volumes of the part involved in learning, and also did more poorly on memory tests than alcoholics who didn’t have seizures.

4. Brain function

a. What does smaller brain volume and loss of brain cells mean in terms of brain functioning? To answer this question, we used a technique called FMRI that allows us to see what brain regions are “active” while a person is doing a certain task. While in the MRI scanner, we show pictures, movies, or questions on a screen that the participant can see. While they are performing the task on the screen, the scanner takes pictures of their brain every 3 seconds. This allows us to make a “movie” of their brain activity so we can tell which regions are active while they are doing the task.

b. What brain regions underlie the cognitive difficulties associated with heavy drinking? Since alcoholic individuals usually have spatial and memory problems, we wanted to understand how the brain responds to a spatial memory task. While people were in the scanner, we asked them to do a task where they had to remember the locations of figures on the screen. The front and upper back regions of the brain are usually involved in this type of memory and spatial task.

c. These are pictures of the brain taken from fMRI. This is a statistical comparison of a group of alcoholics and a group of controls. There is a top view and a side view. The warm colors are areas where the alcoholics had more activation than the controls. In the back part of the brain, where we expect people to have a brain response to the task, the alcoholics had more brain response. This suggests that in early stages of abstinence, the brain may need to use more resources, or “work harder” to maintain performance.

5. Recovery of deficits

a. What about recovery? We brought back a group of guys who had been sober for about two years. Here are the results. You can see that the guys in treatment had a lot more activation than the guys who had maintained sobriety for 2 years.

b. This image, contrasting long-term recovering alcoholics versus non drinkers shows relatively few differences in brain function.

c. Recovery of brain structure. The brain is pretty resilient to damage. We scanned a guy who came into the VA’s alcohol drug treatment program a couple years ago. After 18 months of sobriety, we scanned him again. You can see that just 18 months after stopping drinking, his brain actually unshrunk.

B. Marijuana

1. Thinking abilities.

a. Changes may subside within a month of abstinence, at least in adults.

b. However, as many users use daily or near daily, this is still important as these problems affect functioning at work and school and in their day to day lives.

2. Brain structure and function. Less evidence of persisting problems.

C. Stimulants

1. Thinking abilities

a. Learning & Memory—especially verbal information, like a grocery list or a story—may make it hard to remember what happened in a day, or what was learned in treatment

b. Spatial skills—especially things that take planning, like doing a puzzle or reading a map, following directions to a place

c. Motor skills—playing sports, driving; fine motor skills (speeded manual dexterity)

d. Working memory – your ability to do math in your head, or manipulate information held in memory

e. Executive Functioning is the ability to integrate past experience and future anticipation into a plan for present action. Planning—coming up with a strategy; Switching tasks; Making decisions based on past experience and anticipation of future; Impulsivity.

f. These skills are compromised in drug users, since the brain reward circuitry is off-balance—it makes it hard to plan for future rewards when an immediate reward is availableàcircular

2. Brain structure and function.

a. Little evidence so far. Hippocampal reduction related to poorer memory performance (Source: Thompson et al., (2004). J Neurosci.; see also Jernigan.)

b. How does brain structure injury affect brain functioning? This is a different technique that measures resting blood flow in the brain. Top view: Note change in front of brain—area related to “executive functions” not getting enough blood

3. Recovery – longitudinal studies are needed, but some recovery appears likely.

D. Thinking problems – especially learning & memory, executive functioning, and attention

III. What can we do about this?

A. Educate patients

B. Adapt treatment

1. Clinicians should understand that patients can’t learn a lot of new material and do extensive planning early in sobriety. Instructions may need to be written, and might ask patients to repeat instructions and advice, to make sure they’ve got it, especially in the first few weeks of sobriety.

2. There is some evidence that cognitive recovery can be facilitated by cognitive rehabilitation

3. Some preliminary suggestion of medicines that could help attenuate cognitive damage

C. Recovery is likely, with abstinence.

1. Most patients will show substantial recovery, although it may not be complete.

2. Chance of complete or near complete recover is best in younger patients who are fairly healthy and haven’t had withdrawal seizures.