Try out PMC Labs and tell us what you think. Learn More. Modern imaging techniques enable researchers to observe drug actions and consequences as they occur and persist in the brains of abusing and addicted individuals. This article presents the five most commonly used techniques, explains how each produces images, and describes how researchers interpret them. The authors give examples of key findings illustrating how each technique has extended and deepened our knowledge of the neurobiological bases of drug abuse and addiction, and they address potential clinical and therapeutic applications.
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Scientific advances over the last quarter century have established that drug addiction is a chronic brain disease Leshner, Clinicians may one day—perhaps sooner rather than later—use brain imaging to assess addiction, to as patients to appropriate care interventions, and to monitor response to therapy. Individually, the techniques yield knowledge of brain anatomy and tissue composition; biochemical, physiological, and functional processes; neurotransmitter activity; energy utilization and blood flow; and drug distribution and kinetics.
Together and in combination with other research techniques, they inform a multidimensional understanding of the complex disease that is drug abuse and addiction. It also can demonstrate the presence of abnormal tissue and changes in tissue composition. The prefrontal cortex is the focal area for cognition and planning.
The VTA, NAc, amygdala, and hippocampus are major components of the limbic system, which coordinates drives, emotions, and memories. A structural MRI image is a picture of water molecules in a cross section or area of the brain. The technique takes advantage of the fact that different types of tissues contain different amounts of water.
For example, of the two types of tissues that make up most of the brain, gray matter, which comprises mostly cell nuclei, is roughly 80 percent water, while white matter, which consists mainly of connecting fibers between cells, is about 70 percent water Neeb, Zilles, and Shah, Structural MRI images show these differences in the water content as different tones of gray.
To make structures of interest stand out better, scientists often use contrast agents to heighten the differences. Scientists reading an MRI can readily distinguish gray and white matter and other types of tissue—both normal, such as blood vessels, and abnormal, such as tumors—by their different shading and contrast with surrounding areas Figure 2. An MRI machine can be compared to a camera, but one that registers radiofrequency energy reflected from the hydrogen atoms in water molecules instead of light from visible objects.
The machine itself supplies the radiofrequency energy, somewhat analogous to the way a camera flashbulb bounces light off a scene and then captures the reflected light on film.
Normal healthy brain
Next, the machine emits a brief pulse of radiofrequency energy. For the fraction of a second that the pulse lasts, this subset of protons holds on to the energy.
When the pulse ends, they shed it. Structural MRI studies have demonstrated that chronic drug exposure can enlarge or shrink some regions of the brain. These findings have helped scientists home in on the regions where drugs exert important effects.
The frontal cortex is a brain region that supports logical thinking, goal setting, planning, and self-control. A structural MRI study found that individuals with a history of abusing multiple substances have smaller prefrontal lobes than matched controls Liu et al. This finding adds to growing evidence associating prefrontal abnormalities with abuse of various substances Stapleton et al.
This is (actually, accurately) your brain on drugs
Similar white matter deficits have been found in individuals with other psychiatric disorders that tend to co-occur with substance abuse Schlaepfer et al. Kim and colleagues documented a reduction in gray matter density in the right middle frontal cortex of abstinent methamphetamine abusers Figure 3.
Gray matter was closer to normal in individuals who had been abstinent for more than 6 months than in others with a shorter period of abstinence. In another structural MRI study, cocaine abusers who had been abstinent for 20 days exhibited reduced gray matter density in regions of the frontal cortex.
No differences were found with respect to white matter density Matochik et al.
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The yellow and red area in the central brain view indicates reduced gray matter density in the right middle frontal cortex Kim et al. The same deficit is shown from other perspectives in the flanking views. Investigators using structural MRI have reported diminished cortical gray matter, most prominently in the prefrontal cortex PFCin alcoholic patients in treatment Pfefferbaum et al.
In another study, researchers showed that alcohol-dependent individuals had reduced whole brain, prefrontal cortical, and parietal cortical gray matter compared with controls Fein et al. For a good review on brain imaging in alcoholism, see Mann et al. This is similar to enlarged basal ganglia structures seen in schizophrenic patients who have been treated with typical antipsychotic medications Gur et al. Because typical antipsychotics and psychostimulants both lead to occupation of dopamine receptors in the basal ganglia—the former directly and the latter indirectly, through releasing dopamine—these findings suggest the dopamine and basal ganglia structures are involved in the psychoses that occur in schizophrenia and in psychostimulant abuse.
An analysis of MRI images disclosed that a group of chronic methamphetamine abusers had severe gray matter deficits in the cingulate, limbic, and paralimbic cortices. They also had smaller hippocampi than nonabusers of drugs.
The hippocampus is a key site for memory storage, and the volume decrements correlated with poorer performance on a word recall test Thompson et al. Another MRI study indicated that the amygdala, a brain structure that helps shape our emotional responses to experiences, is relatively small in children of alcoholics Hill et al. This finding might be a clue to the brain sources of vulnerability to alcohol abuse disorders. Researchers read functional MRI images as maps of cellular activity levels in a cross section or area of the brain. In functional MRI studies, researchers compare multiple images, which may be of a single individual or different individuals.
Studies of a single individual taken under varying conditions—for example, at rest and then working on a puzzle, or before and after taking a drug—enable researchers to map which brain regions he or she activates to perform mental tasks e.
Studies of individuals from different groups—for example, drug-addicted and nonaddicted—can reveal differences in the brain regions the two groups use to perform identical tasks or respond to stimuli or exposures. What a functional MRI machine actually detects are changes in the local magnetic field that occur as a result of changes in the ratio of oxygenated to deoxygenated hemoglobin in arterial blood vessels in specific brain regions during a cognitive task.
The rationale for interpreting these changes as cellular activity is that cells in the brain, like those elsewhere in the body, use oxygen as fuel. As they increase their activity, they increase their demand for oxygen, and the arterial blood vessels respond by delivering more oxygenated hemoglobin to the region.
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Like structural MRI, functional MRI produces images by applying a magnetic field and detecting radiofrequency energy from the protons in water molecules. However, functional MRI exploits two additional facts, one biological and one physical:.
Biologically, the more oxygen that cells in a region utilize, the more oxygen-carrying hemoglobin molecules will be found in the blood vessels responsible for supplying them. Physically, hemoglobin molecules that have oxygen molecules attached to them and those that do not exert measurably different effects on the magnetic properties of surrounding tissues.
By tuning the magnets and energy pulses of the MRI machine to capture these differences, researchers produce images in which differences in oxygen content show up as variations in tone or color. This is called blood oxygen level dependent, or BOLD, contrast. The differences in brain activity patterns revealed by functional MRI provide invaluable information on a range of issues.
Studies have correlated regional brain patterns in response to taking a drug with vulnerability to drug abuse, addictive symptoms and behaviors, and long-term cognitive capacity. Researchers have used functional MRI to obtain detailed information about the roles of different brain areas in producing cocaine-induced euphoria and subsequent craving. In one investigation, volunteers given an infusion of cocaine reported a drug rush during the brief period when a set of areas, including the caudate an area of the basal gangliacingulate, and most of the lateral PFC showed higher levels of activity.
Imaging the addicted human brain
Craving correlated positively with activity in these regions Kufahl et al. For example, Wexler and colleagues documented activation of the anterior cingulate cortex, a region associated with emotional processing, while cocaine-addicted subjects watched videotapes containing cocaine-associated cues, even if they did not experience craving Figure 4.
The subjects also showed less activation in the frontal lobe than healthy subjects during the cocaine cue tapes, suggesting that their ability to control their cue responses was inhibited. In one study, methamphetamine dependence and poor decisionmaking correlated with reduced activation in the PFC Paulus et al. In another, investigators discovered that chronic cocaine abusers had abnormally low levels of activity in midline areas of the anterior cingulate that are crucial for cognitive and behavioral control Kaufman et al. Arrows point to the anterior cingulate area, which is activated yellow in cocaine-addicted patients left but not in healthy volunteers right Wexler et al.
Innovative functional MRI studies recently have begun to explore the role of genes in drug abuse. A similar functional MRI study discovered that individuals with a particular variation in the serotonin transporter gene experienced greater activation in the amygdala, a region associated with fear and anxiety, in response to fearful stimuli Hariri et al.
This genetic variation could increase sensitivity to stress and heighten vulnerability to drug abuse.
In addition to creating structural and functional maps of the brain, magnetic resonance technology can be used to detect and measure important chemical contents within the brain. To be visible in an MRS image, a chemical must respond in a unique way to magnetization and energy stimulation, and it must be present in relatively high concentrations in the millimolar range.
MRS scans reveal the location and concentrations of target chemicals in the brain tissues Ross, Kreis, and Ernst, Among chemicals naturally present in the brain, two that can be studied with MRS include N-acetylaspartate NAAwhich researchers use as a gauge of neuronal cell health Birken and Oldendorf,and myoinositol, which is primarily present in support cells, called glia Brand, Richter-Landsberg, and Leibfritz,and thus provides an index of the health of glial cells.
Among substances of abuse that penetrate the brain after being ingested or administered, alcohol is readily apparent with MRS Hetherington et al. In MRS, the magnetic pulses and radiofrequency energy are used to stimulate the nucleus of particular elements e.
The sum of all these als is recorded and then analyzed using specialized computer programs to separate the als corresponding to each metabolite. The can be displayed as various metabolite peaks on a spectrum. Researchers have used MRS to identify drug-related biochemical changes that indicate damage to the health and function of brain cells.