High-Field Functional MRI of Human Euphoria

Drug abuse and addiction pose major health problems to individuals worldwide. The brain biology of drug addiction is thought to involve a variety of brain structures that evolved to have a role in natural rewards, such as finding food or having sex. Drugs of abuse are used in part because they make an individual "high" or euphoric when they are taken.

Much of the evidence learned thus far about drug addiction suggests that regions of the brain, including the ventral tegmental area which uses the neurotransmitter dopamine, and the nucleus accumbens have a major role in reward and the experience of euphoria. Additional evidence indicates that humans reliably develop a high voltage electroencephalographic (EEG) waveform in the alpha band during the experience of euphoria. We propose to use the functional magnetic resonance imaging (fMRI) blood oxygen level dependent (BOLD) method to study the regional changes in brain activity during the experience of euphoria in humans.

Human volunteers will be screened for medical or psychiatric problems that prevent them from participating in the study. Subjects will then be given a dose of dextroamphetamine, and the ongoing activity in their brain will be studied with fMRI BOLD. Subjects will be asked to indicate when they feel euphoric, and we will use statistical analysis to determine which brain regions seem to produce the euphoria, and how they are interconnected to other brain regions. In the future, we plan to combine this method with other methods, including EEG, so that we might begin to develop a detailed understanding of the temporal and spatial changes in brain activity during the euphoric experience. Additionally, we plan to investigate how different drugs of abuse, and some medications that might interfere with the effects of drugs of abuse, affect the human reward system. Eventually, we believe that a better understanding of the brain structures that allow us to get high, and become addicted, will lead to improved awareness and treatment for substance abuse.

The brain's reward system mediates behavioral activities related to acquiring natural rewards. In addition, the reward system is the principal neural system targeted by drugs of abuse. Many contemporary public health issues, including obesity, overpopulation, tobacco use, alcoholism, and other drug-use disorders are strongly linked to reward system function and dysfunction. While a variety of complicated environmental and biological factors converge in determining an individual's risk of substance abuse and dependence, the final common events leading to an individual's drug use reside within the brain's neural circuitry.

The reportable subjective awareness of mood states, including euphoria, is a uniquely human experience. The behavioral response to drug ingestion or natural rewards is complex, consisting of conscious components such as the experience of euphoria or mood change and unconscious components such as the encoding of environmental information during conditioned place preference acquisition, or a mixture of the two. An example of a mixture of conscious components and unconscious components is psychomotor activation leading to increased movement and the awareness of increased energy. Coincident with the transient subjective experience of mood change, the brain undergoes a complex series of alterations in distributed neocortical and subcortical synaptic circuitry, producing long-term adaptations that alter future responses to the presence, and, ultimately, the absence of drug or other rewards. The main goals of this long-term project are the systematic dissection of the neural basis of the brain's reward-response.

The study of the neurobiology of euphoria in humans is part of a long-range effort to employ multimodal techniques to investigate and manipulate neural processes subserving reward system function, and to thereby better understand drug use and dependence and other disorders. Two major questions regarding drug our lab seeks to answer with this project are:  

  1. Why do individuals decide to use a drug in the first case?
  2. Why can't some individuals stop using drugs when they want to?

This study is currently on hold pending data analysis and grant submission.  The initial pilot data for the study employed fMRI BOLD method at 3 Tesla to examine dose and time-dependent effects of d-amphetamine on the induction of euphoria. Subjects were given amphetamine and received sequential mood assessments during scanning. Additional studies are planned to correlate EEG activity with the BOLD response.

Future work issues requiring more detailed study include:

  1. The temporal pattern of activity within specific brain regions
  2. The transmitter specificity of each brain region
  3. The specific contribution of each brain region to specific aspects of the post-drug experience (e.g. dysphoria, craving, conditioned place preference, euphoria, behavioral activation, etc.).