Greater understanding of the brain science underlying impulsivity and its connection to substance use disorder may ultimately improve strategies for prevention and treatment. This study used brain imaging to investigate links between impulsivity and amphetamine use disorder and the role of sex in influencing the strength of these relationships.
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Impulsivity — a cognitive process related to poor self-regulation or “leaping before you look” instead of “looking before you leap” — is consistently associated with substance use disorders. However, impulsivity is best understood across multiple levels of complexity, from differences in brain function to momentary changes in behavior to stable long-term (even lifetime) personality differences among individuals. Owing to this complexity, research can help illuminate the role of impulsivity in substance use disorders, including conditions like amphetamine use disorder, and its implications for treatment and recovery.
A key insight into understanding the neuroscience of impulsivity and the association between impulsivity and substance use is the potential differences between males and females.
Prior work has widely shown that males often appear more impulsive than their female peers across multiple “levels of analysis,” including both behavioral assessments and brain imaging. The exact reasons behind these sex differences are unclear, but likely have complex contributions from biology, individuals’ environment, and broader society (e.g., sex-specific narratives highlighted and reinforced by mainstream and social media). While researchers and clinicians have explored these questions in many forms of substance use, like alcohol use disorder, more limited research has examined sex differences in impulsivity in amphetamine use disorder.
Like other substance use disorders, amphetamine use disorder is often chronic and relapsing and can continue to escalate, despite serious potential psychological and physical consequences. The prevalence of amphetamine use disorder and related overdoses have dramatically increased over the past several years, at least doubling between 2015-2019. However, like impulsivity, amphetamine use disorder prevalence and treatment outcomes show important differences between males and females, what scientists, often refer to as “sexual dimorphism.” Nevertheless, little research has examined the underlying brain differences, or the link to impulsivity, that may distinguish male and female individuals with amphetamine use disorder. This could have important implications for the unique treatment and recovery needs of males and females.
Using a subsample of participants from a larger existing database, this study measured functional brain metrics (i.e., functional magnetic resonance imaging [fMRI]) and behaviors associated with impulsivity in adults with and without amphetamine use disorder.
This study included 49 adults with amphetamine use disorder and 90 adults without amphetamine use disorder from a larger existing neuroimaging sample of participants recruited from the community (Tulsa 1000 study). Participants in the amphetamine use disorder group were required to meet criteria for amphetamine dependence or amphetamine use disorder, according to DSM-IV and DSM-5 definitions, respectively, and report amphetamines as their current primary substance used. Participants included in this group were allowed to have co-occurring major depressive disorder as well as anxiety, stress, and substance use disorders. Participants in the non-amphetamine use disorder group could not meet criteria for any past-year DSM-IV or DSM-5 disorder diagnoses other than nicotine use disorder or past, but not current, major depressive disorder. Amphetamine use disorder and non-amphetamine use disorder groups selected for this analysis did not differ in the proportion of men and women or average ages within each group. Other details on the historical patterns of amphetamines and other substance use were not reported.
Amphetamine use disorder and non-amphetamine use disorder groups, as part of the larger Tulsa 1000 sample, each completed functional Magnetic Resonance Imagining (fMRI) scan while completing a Stop Signal Task (SST) that captures brain patterns thought to be associated with impulsivity. In the SST, participants are told to respond as quickly as possible to a regularly presented visual stimulus. Then after getting used to making this automatic response, a tone (“signal”) is intermittently played, and the participants must withhold “stop” their automatic response. Participants’ ability to withhold this automatic response is thought to be related to impulsivity. As an observational cross-sectional study, each participant completed this scan once. The research team confirmed that no substances, amphetamines or otherwise, were detected prior to the fMRI scan. Participants also completed a standard self-report measure of impulsivity based on five personality characteristics (UPPS-P scale).
The study examined potential brain differences between amphetamine use disorder and non-amphetamine use disorder groups during the SST and in the context of a self-report measure of impulsivity. They also tested whether the relative magnitude of these differences between groups on impulsivity measures varied between males and females.
Behavioral and neural differences associated with impulsivity in amphetamine use disorder.
Consistent with prior reports and broader theories of addiction, participants with amphetamine use disorder had higher scores of self-reported impulsivity than participants without amphetamine use disorder. This was observed across multiple different self-reported impulsivity assessments. There was also some evidence for differences between males and females with and without amphetamine use disorder on impulsivity metrics, but these were less consistent across assessments.
In parallel to self-reported assessments of impulsivity, multiple brain regions showed differences between the amphetamine use disorder and non-amphetamine use disorder groups, both in the aggregate of the full group (“group main effect”) and when comparing only males or females (“group by sex interaction”).
Evidence for both increased and decreased functional activation (the relative magnitude of brain activity during the SST task captured by the brain scan) was seen in adults with amphetamine use disorder, relative to non-amphetamine use disorder adults.
Sex differences in impulsivity-related brain activation among adults with amphetamine use disorder.
The largest and most consistent effects distinguishing amphetamine use disorder and non-amphetamine use disorder groups in the context of the SST were observed in the brain region called the insula, which has been previously widely implicated in impulse control and the joint regulation of emotional and cognitive processes. Additional functional activation differences were found in the amygdala, a brain region associated with emotion processing and regulation, and the nucleus accumbens, a core region in the brain’s reward circuit.
As a group, participants with amphetamine use disorder displayed higher functional activation of the insula when completing the SST, possibly suggesting a compensatory mechanism of heightened impulse control is necessary to complete the same task as the non-amphetamine use disorder group (Figure 2). However, when examining the relative difference specifically between males and females, some aspects of this “hyper-activation” of the insula appeared to be only present in males with amphetamine use disorder, but not females.
Figure 2. Localization of general functional brain differences between participants with and without amphetamine use disorder.
Adults with amphetamine use disorder appear to display functional differences in brain regions associated with impulsivity, both in the aggregate and when considering male participants only.
These brain differences linked to impulsivity in amphetamine use disorder, and their potential sex-specific pattern, fit with long-standing broader research linking impulsivity to substance use disorders that may likewise be sex-specific. However, as a cross-sectional study, where participants were only assessed at one timepoint, causality and directionality between amphetamine use disorder, impulsivity, and brain imaging measures remain inconclusive.
This study and others using brain imaging techniques like fMRI can further our understanding of the origins and treatment of substance use disorders. Owing to the differences between males and females in substance use presentations and impulsivity—a key factor in risk for, and the treatment of, substance use disorders—studies that examine potential sex differences in brain function associated with addiction are particularly important. Towards this goal, the current study demonstrated that functional brain differences in a key impulse control related brain region (insula) associated with amphetamine use disorder may, at least in part, be larger in males compared to females. In principle, this provides some indication that these brain regions may one day be useful to help personalize treatment and recovery support plans (often called “personalized medicine”). There are, however, limitations of this work worth noting (see below), and brain imaging in substance use and recovery remains a relatively new field of scientific research.
Amphetamine use disorder appears to be associated with differences in functional activation in brain regions associated with impulsivity. In certain cases, these effects were larger in males than females, suggesting the connection between impulsivity and amphetamine use disorder is stronger in men. This work, along with a growing number of previous studies, provides hypotheses to test in future work that may ultimately help tailor treatments for amphetamine use disorder and other substance use disorders (often called “personalized medicine”) or help measure response to treatment and other recovery-related progress. However, brain imaging in substance use disorders remains a relatively new field of scientific research. This work can therefore contribute to scientific knowledge regarding the neuroscience of substance use disorders but not yet directly influence treatment.
Stewart, J. L., Burrows, K., Davis, C. B., Wilhelm, R. A., McNaughton, B. A., Kuplicki, R., . . . & White, E. J. (2023). Impulsivity in amphetamine use disorder: Examination of sex differences. Addiction, 118(9), 1787-1800. doi: 10.1111/add.16225
l
Impulsivity — a cognitive process related to poor self-regulation or “leaping before you look” instead of “looking before you leap” — is consistently associated with substance use disorders. However, impulsivity is best understood across multiple levels of complexity, from differences in brain function to momentary changes in behavior to stable long-term (even lifetime) personality differences among individuals. Owing to this complexity, research can help illuminate the role of impulsivity in substance use disorders, including conditions like amphetamine use disorder, and its implications for treatment and recovery.
A key insight into understanding the neuroscience of impulsivity and the association between impulsivity and substance use is the potential differences between males and females.
Prior work has widely shown that males often appear more impulsive than their female peers across multiple “levels of analysis,” including both behavioral assessments and brain imaging. The exact reasons behind these sex differences are unclear, but likely have complex contributions from biology, individuals’ environment, and broader society (e.g., sex-specific narratives highlighted and reinforced by mainstream and social media). While researchers and clinicians have explored these questions in many forms of substance use, like alcohol use disorder, more limited research has examined sex differences in impulsivity in amphetamine use disorder.
Like other substance use disorders, amphetamine use disorder is often chronic and relapsing and can continue to escalate, despite serious potential psychological and physical consequences. The prevalence of amphetamine use disorder and related overdoses have dramatically increased over the past several years, at least doubling between 2015-2019. However, like impulsivity, amphetamine use disorder prevalence and treatment outcomes show important differences between males and females, what scientists, often refer to as “sexual dimorphism.” Nevertheless, little research has examined the underlying brain differences, or the link to impulsivity, that may distinguish male and female individuals with amphetamine use disorder. This could have important implications for the unique treatment and recovery needs of males and females.
Using a subsample of participants from a larger existing database, this study measured functional brain metrics (i.e., functional magnetic resonance imaging [fMRI]) and behaviors associated with impulsivity in adults with and without amphetamine use disorder.
This study included 49 adults with amphetamine use disorder and 90 adults without amphetamine use disorder from a larger existing neuroimaging sample of participants recruited from the community (Tulsa 1000 study). Participants in the amphetamine use disorder group were required to meet criteria for amphetamine dependence or amphetamine use disorder, according to DSM-IV and DSM-5 definitions, respectively, and report amphetamines as their current primary substance used. Participants included in this group were allowed to have co-occurring major depressive disorder as well as anxiety, stress, and substance use disorders. Participants in the non-amphetamine use disorder group could not meet criteria for any past-year DSM-IV or DSM-5 disorder diagnoses other than nicotine use disorder or past, but not current, major depressive disorder. Amphetamine use disorder and non-amphetamine use disorder groups selected for this analysis did not differ in the proportion of men and women or average ages within each group. Other details on the historical patterns of amphetamines and other substance use were not reported.
Amphetamine use disorder and non-amphetamine use disorder groups, as part of the larger Tulsa 1000 sample, each completed functional Magnetic Resonance Imagining (fMRI) scan while completing a Stop Signal Task (SST) that captures brain patterns thought to be associated with impulsivity. In the SST, participants are told to respond as quickly as possible to a regularly presented visual stimulus. Then after getting used to making this automatic response, a tone (“signal”) is intermittently played, and the participants must withhold “stop” their automatic response. Participants’ ability to withhold this automatic response is thought to be related to impulsivity. As an observational cross-sectional study, each participant completed this scan once. The research team confirmed that no substances, amphetamines or otherwise, were detected prior to the fMRI scan. Participants also completed a standard self-report measure of impulsivity based on five personality characteristics (UPPS-P scale).
The study examined potential brain differences between amphetamine use disorder and non-amphetamine use disorder groups during the SST and in the context of a self-report measure of impulsivity. They also tested whether the relative magnitude of these differences between groups on impulsivity measures varied between males and females.
Behavioral and neural differences associated with impulsivity in amphetamine use disorder.
Consistent with prior reports and broader theories of addiction, participants with amphetamine use disorder had higher scores of self-reported impulsivity than participants without amphetamine use disorder. This was observed across multiple different self-reported impulsivity assessments. There was also some evidence for differences between males and females with and without amphetamine use disorder on impulsivity metrics, but these were less consistent across assessments.
In parallel to self-reported assessments of impulsivity, multiple brain regions showed differences between the amphetamine use disorder and non-amphetamine use disorder groups, both in the aggregate of the full group (“group main effect”) and when comparing only males or females (“group by sex interaction”).
Evidence for both increased and decreased functional activation (the relative magnitude of brain activity during the SST task captured by the brain scan) was seen in adults with amphetamine use disorder, relative to non-amphetamine use disorder adults.
Sex differences in impulsivity-related brain activation among adults with amphetamine use disorder.
The largest and most consistent effects distinguishing amphetamine use disorder and non-amphetamine use disorder groups in the context of the SST were observed in the brain region called the insula, which has been previously widely implicated in impulse control and the joint regulation of emotional and cognitive processes. Additional functional activation differences were found in the amygdala, a brain region associated with emotion processing and regulation, and the nucleus accumbens, a core region in the brain’s reward circuit.
As a group, participants with amphetamine use disorder displayed higher functional activation of the insula when completing the SST, possibly suggesting a compensatory mechanism of heightened impulse control is necessary to complete the same task as the non-amphetamine use disorder group (Figure 2). However, when examining the relative difference specifically between males and females, some aspects of this “hyper-activation” of the insula appeared to be only present in males with amphetamine use disorder, but not females.
Figure 2. Localization of general functional brain differences between participants with and without amphetamine use disorder.
Adults with amphetamine use disorder appear to display functional differences in brain regions associated with impulsivity, both in the aggregate and when considering male participants only.
These brain differences linked to impulsivity in amphetamine use disorder, and their potential sex-specific pattern, fit with long-standing broader research linking impulsivity to substance use disorders that may likewise be sex-specific. However, as a cross-sectional study, where participants were only assessed at one timepoint, causality and directionality between amphetamine use disorder, impulsivity, and brain imaging measures remain inconclusive.
This study and others using brain imaging techniques like fMRI can further our understanding of the origins and treatment of substance use disorders. Owing to the differences between males and females in substance use presentations and impulsivity—a key factor in risk for, and the treatment of, substance use disorders—studies that examine potential sex differences in brain function associated with addiction are particularly important. Towards this goal, the current study demonstrated that functional brain differences in a key impulse control related brain region (insula) associated with amphetamine use disorder may, at least in part, be larger in males compared to females. In principle, this provides some indication that these brain regions may one day be useful to help personalize treatment and recovery support plans (often called “personalized medicine”). There are, however, limitations of this work worth noting (see below), and brain imaging in substance use and recovery remains a relatively new field of scientific research.
Amphetamine use disorder appears to be associated with differences in functional activation in brain regions associated with impulsivity. In certain cases, these effects were larger in males than females, suggesting the connection between impulsivity and amphetamine use disorder is stronger in men. This work, along with a growing number of previous studies, provides hypotheses to test in future work that may ultimately help tailor treatments for amphetamine use disorder and other substance use disorders (often called “personalized medicine”) or help measure response to treatment and other recovery-related progress. However, brain imaging in substance use disorders remains a relatively new field of scientific research. This work can therefore contribute to scientific knowledge regarding the neuroscience of substance use disorders but not yet directly influence treatment.
Stewart, J. L., Burrows, K., Davis, C. B., Wilhelm, R. A., McNaughton, B. A., Kuplicki, R., . . . & White, E. J. (2023). Impulsivity in amphetamine use disorder: Examination of sex differences. Addiction, 118(9), 1787-1800. doi: 10.1111/add.16225
l
Impulsivity — a cognitive process related to poor self-regulation or “leaping before you look” instead of “looking before you leap” — is consistently associated with substance use disorders. However, impulsivity is best understood across multiple levels of complexity, from differences in brain function to momentary changes in behavior to stable long-term (even lifetime) personality differences among individuals. Owing to this complexity, research can help illuminate the role of impulsivity in substance use disorders, including conditions like amphetamine use disorder, and its implications for treatment and recovery.
A key insight into understanding the neuroscience of impulsivity and the association between impulsivity and substance use is the potential differences between males and females.
Prior work has widely shown that males often appear more impulsive than their female peers across multiple “levels of analysis,” including both behavioral assessments and brain imaging. The exact reasons behind these sex differences are unclear, but likely have complex contributions from biology, individuals’ environment, and broader society (e.g., sex-specific narratives highlighted and reinforced by mainstream and social media). While researchers and clinicians have explored these questions in many forms of substance use, like alcohol use disorder, more limited research has examined sex differences in impulsivity in amphetamine use disorder.
Like other substance use disorders, amphetamine use disorder is often chronic and relapsing and can continue to escalate, despite serious potential psychological and physical consequences. The prevalence of amphetamine use disorder and related overdoses have dramatically increased over the past several years, at least doubling between 2015-2019. However, like impulsivity, amphetamine use disorder prevalence and treatment outcomes show important differences between males and females, what scientists, often refer to as “sexual dimorphism.” Nevertheless, little research has examined the underlying brain differences, or the link to impulsivity, that may distinguish male and female individuals with amphetamine use disorder. This could have important implications for the unique treatment and recovery needs of males and females.
Using a subsample of participants from a larger existing database, this study measured functional brain metrics (i.e., functional magnetic resonance imaging [fMRI]) and behaviors associated with impulsivity in adults with and without amphetamine use disorder.
This study included 49 adults with amphetamine use disorder and 90 adults without amphetamine use disorder from a larger existing neuroimaging sample of participants recruited from the community (Tulsa 1000 study). Participants in the amphetamine use disorder group were required to meet criteria for amphetamine dependence or amphetamine use disorder, according to DSM-IV and DSM-5 definitions, respectively, and report amphetamines as their current primary substance used. Participants included in this group were allowed to have co-occurring major depressive disorder as well as anxiety, stress, and substance use disorders. Participants in the non-amphetamine use disorder group could not meet criteria for any past-year DSM-IV or DSM-5 disorder diagnoses other than nicotine use disorder or past, but not current, major depressive disorder. Amphetamine use disorder and non-amphetamine use disorder groups selected for this analysis did not differ in the proportion of men and women or average ages within each group. Other details on the historical patterns of amphetamines and other substance use were not reported.
Amphetamine use disorder and non-amphetamine use disorder groups, as part of the larger Tulsa 1000 sample, each completed functional Magnetic Resonance Imagining (fMRI) scan while completing a Stop Signal Task (SST) that captures brain patterns thought to be associated with impulsivity. In the SST, participants are told to respond as quickly as possible to a regularly presented visual stimulus. Then after getting used to making this automatic response, a tone (“signal”) is intermittently played, and the participants must withhold “stop” their automatic response. Participants’ ability to withhold this automatic response is thought to be related to impulsivity. As an observational cross-sectional study, each participant completed this scan once. The research team confirmed that no substances, amphetamines or otherwise, were detected prior to the fMRI scan. Participants also completed a standard self-report measure of impulsivity based on five personality characteristics (UPPS-P scale).
The study examined potential brain differences between amphetamine use disorder and non-amphetamine use disorder groups during the SST and in the context of a self-report measure of impulsivity. They also tested whether the relative magnitude of these differences between groups on impulsivity measures varied between males and females.
Behavioral and neural differences associated with impulsivity in amphetamine use disorder.
Consistent with prior reports and broader theories of addiction, participants with amphetamine use disorder had higher scores of self-reported impulsivity than participants without amphetamine use disorder. This was observed across multiple different self-reported impulsivity assessments. There was also some evidence for differences between males and females with and without amphetamine use disorder on impulsivity metrics, but these were less consistent across assessments.
In parallel to self-reported assessments of impulsivity, multiple brain regions showed differences between the amphetamine use disorder and non-amphetamine use disorder groups, both in the aggregate of the full group (“group main effect”) and when comparing only males or females (“group by sex interaction”).
Evidence for both increased and decreased functional activation (the relative magnitude of brain activity during the SST task captured by the brain scan) was seen in adults with amphetamine use disorder, relative to non-amphetamine use disorder adults.
Sex differences in impulsivity-related brain activation among adults with amphetamine use disorder.
The largest and most consistent effects distinguishing amphetamine use disorder and non-amphetamine use disorder groups in the context of the SST were observed in the brain region called the insula, which has been previously widely implicated in impulse control and the joint regulation of emotional and cognitive processes. Additional functional activation differences were found in the amygdala, a brain region associated with emotion processing and regulation, and the nucleus accumbens, a core region in the brain’s reward circuit.
As a group, participants with amphetamine use disorder displayed higher functional activation of the insula when completing the SST, possibly suggesting a compensatory mechanism of heightened impulse control is necessary to complete the same task as the non-amphetamine use disorder group (Figure 2). However, when examining the relative difference specifically between males and females, some aspects of this “hyper-activation” of the insula appeared to be only present in males with amphetamine use disorder, but not females.
Figure 2. Localization of general functional brain differences between participants with and without amphetamine use disorder.
Adults with amphetamine use disorder appear to display functional differences in brain regions associated with impulsivity, both in the aggregate and when considering male participants only.
These brain differences linked to impulsivity in amphetamine use disorder, and their potential sex-specific pattern, fit with long-standing broader research linking impulsivity to substance use disorders that may likewise be sex-specific. However, as a cross-sectional study, where participants were only assessed at one timepoint, causality and directionality between amphetamine use disorder, impulsivity, and brain imaging measures remain inconclusive.
This study and others using brain imaging techniques like fMRI can further our understanding of the origins and treatment of substance use disorders. Owing to the differences between males and females in substance use presentations and impulsivity—a key factor in risk for, and the treatment of, substance use disorders—studies that examine potential sex differences in brain function associated with addiction are particularly important. Towards this goal, the current study demonstrated that functional brain differences in a key impulse control related brain region (insula) associated with amphetamine use disorder may, at least in part, be larger in males compared to females. In principle, this provides some indication that these brain regions may one day be useful to help personalize treatment and recovery support plans (often called “personalized medicine”). There are, however, limitations of this work worth noting (see below), and brain imaging in substance use and recovery remains a relatively new field of scientific research.
Amphetamine use disorder appears to be associated with differences in functional activation in brain regions associated with impulsivity. In certain cases, these effects were larger in males than females, suggesting the connection between impulsivity and amphetamine use disorder is stronger in men. This work, along with a growing number of previous studies, provides hypotheses to test in future work that may ultimately help tailor treatments for amphetamine use disorder and other substance use disorders (often called “personalized medicine”) or help measure response to treatment and other recovery-related progress. However, brain imaging in substance use disorders remains a relatively new field of scientific research. This work can therefore contribute to scientific knowledge regarding the neuroscience of substance use disorders but not yet directly influence treatment.
Stewart, J. L., Burrows, K., Davis, C. B., Wilhelm, R. A., McNaughton, B. A., Kuplicki, R., . . . & White, E. J. (2023). Impulsivity in amphetamine use disorder: Examination of sex differences. Addiction, 118(9), 1787-1800. doi: 10.1111/add.16225
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