A new study proposes that research into the discrete roles played by the brain’s two hemispheres could yield important and actionable insights into drug use and addiction. Dr. Harold Gordon, of NIDA’s Epidemiology Research Branch, marshaled several lines of evidence indicating that two risk factors for substance use, impulsivity and craving, primarily reflect activity in the right and left hemispheres, respectively.
Dr. Gordon compiled scores of published reports of functional magnetic resonance imaging (fMRI) studies that provided data on brain activity in the right and left hemispheres during:
- Go/no-go and stop-signal tests, both of which assess subjects’ ability to resist impulses to repeat a learned response when it is no longer appropriate
- Cue-induced craving protocols, which measure the intensity of drug users’ craving in response to drug-associated images, texts, or other environmental cues
Dr. Gordon computed laterality, defined as the difference in peak activation levels between the hemispheres, while test subjects performed each test or protocol.
Participants in 27 fMRI studies of impulsivity exhibited right laterality, indicating that they primarily activated neurons in the right hemisphere to try to resist impulsive responses. When Dr. Gordon calculated laterality in regional structures, he found that more activity peaks occurred in several areas of the right hemisphere, including the dorsolateral prefrontal cortex and the insula. Right laterality was seen for both the stop-signal test and the go/no-go test in the anterior cingulate, but only for the stop-signal test in the orbitofrontal cortex (OFC) (see Figure 1). This difference suggests that the two tests measure different aspects of impulsivity. The OFC and anterior cingulate underpin reward valuation and emotional regulation.
Patients’ craving responses to drug cues were associated with left laterality when averaged across all 48 craving studies that Dr. Gordon reviewed, suggesting that neural activity in the left hemisphere primarily drives these responses. This pattern of predominantly left activation during cue-induced craving held among study participants who used cocaine, heroin, marijuana, or alcohol. It also was seen, interestingly, with cue-induced craving for food, but not for craving related to computer gaming (see Figure 2).
Findings from fMRI studies of smokers reinforced the link between craving and left laterality. When all the studies of smokers’ craving were averaged together, there was no left/right asymmetry in activation. However, in the studies where smokers were not allowed to smoke for a day before fMRI measurements, the results showed left laterality similar to those for users of the other substances; while in studies when smokers were allowed to smoke before the measurements, the results showed right laterality.
Neurotransmitters and Structural Organization
Dr. Gordon cites previous research that, parallel to the right/left dichotomy in brain activation during impulsivity and craving, has linked:
- inhibitory responses and avoidance behaviors to neurotransmitter activity in the right hemisphere and appetitive responses, and
- approach behaviors to neurotransmitter activity in the left hemisphere.
Dr. Gordon says that these relationships may be important for understanding and ultimately managing drug use disorders.
Among the neurotransmitter studies, one associated dopamine D2 receptor binding in the right hemisphere with motivation to avoid punishment, and greater D2 binding in the left hemisphere with motivation to seek rewards. Other studies have suggested right hemisphere laterality for serotonin activation, which could underlie emotional processing. A few studies, primarily done in rodents, indicate that the neurotransmitter norepinephrine is related to left hemisphere laterality and reward.
Other studies have demonstrated inter-hemisphere differences in structural organization and functional connectivity. A few of these have linked the differences to craving and impulsivity.
Dr. Gordon says that elucidation of how the right and left hemispheres differ and interact in activation, structural organization, and neurotransmitter activity could yield new insights into craving, impulsivity, and other brain mechanisms involved in drug use and addiction. Such knowledge could lead to new prevention and treatment interventions. They might be particularly useful for therapies such as transcranial magnetic stimulation, which, when applied to the left hemisphere but not the right has been shown to reduce craving in smokers and users of cocaine.
- Text Description of Figure 1
The figure shows two bar graphs indicating activation in the right brain hemisphere in response to go/no-go and stop-signal tests. The vertical (y-) axis shows percent greater activation in the right hemisphere and the horizontal (x-) axis the activated brain area. The left graph shows the results for brain areas with similar laterality for both tests, and the right graph displays the results for areas that differed in right laterality for both tests. As shown in the left graph, the area containing the dorsolateral prefrontal cortex showed about 35 percent activation in response to the go/no-go signal test and about 43 percent activation in response to the stop-signal test, and the insula showed about 55 percent activation in response to the go/no-go signal test and about 73 percent activation in response to the stop-signal test. As shown in the right graph, the area containing the orbitofrontal cortex showed no activation in response to the go/no-go signal test and just under a 100 percent activation in response to the stop-signal test, and the area containing the anterior cingulate showed about 23 percent activation in response to the go/no-go signal test and about 48 percent activation in response to the stop-signal test.
- Text Description of Figure 2
The figure shows a bar graph indicating activation in the left hemisphere of the brain relative to activation in the right hemisphere in response to craving. The vertical (y-) axis shows percent greater activation in the left hemisphere and the horizontal (x-) axis the type of craving. As shown in the graph, the percent greater activation in the left hemisphere in response to craving was about 18 percent for cocaine, 14 percent for food, 13 percent for nicotine (in deprived smokers), 10 percent for alcohol, 5 percent for heroin, 4 percent for marijuana, and 1 percent for gaming.
See a video of Dr. Gordon talking about brain laterality in addiction.
- Gordon, H.W. Laterality of Brain Activation for Risk Factors of Addiction. Current Drug Abuse Reviews 9(1), 2016. Abstract