A specific neural substrate predicting current and future impulsivity in young adults

Impulsivity, characterized by rash actions with negative consequences, is prevalent among young adults and contributes significantly to various psychiatric disorders such as bipolar disorder, depressive disorders, ADHD, and borderline personality disorder. Young adulthood, a period of significant neural development and social transition, marks the emergence of many mental health problems. Neuroimaging studies suggest a role for altered amygdala and PFC activity in impulsivity, but the specificity of these neural patterns to impulsivity versus other affective and anxiety symptoms remains unclear. This study aims to identify objective neural markers of impulsivity, differentiating them from markers of anhedonia, affective, and anxiety symptoms. By focusing on the amygdala and PFC, key regions involved in emotion processing and regulation, the study aims to provide targets for interventions to prevent or mitigate the development of impulsivity and future psychiatric disorders during this critical developmental period. Previous research has indicated a pattern of heightened amygdala activity and altered PFC activity and amygdala-PFC connectivity in impulsivity. However, these studies often had small sample sizes, lacked examination of different impulsivity subscales, and did not employ a transdiagnostic approach. Moreover, other symptoms such as anhedonia, and affective and anxiety symptoms share similar neural correlates, making it crucial to disentangle their neural signatures from that of impulsivity. The UPPS-P Impulsive Behavior Scale, a comprehensive and well-validated measure of impulsivity, was employed to assess impulsivity, along with measures for anhedonia, depression, anxiety, and mania/hypomania. The current study aims to address these limitations by investigating a large transdiagnostic sample of young adults, examining neural activity in relation to different impulsivity subscales, and controlling for other co-occurring symptoms.

Existing literature suggests a link between impulsivity and heightened subcortical activity, particularly in the amygdala, coupled with altered PFC activity and amygdala-PFC functional connectivity. Studies using the UPPS-P Impulsivity Scale and other measures have shown associations between impulsivity and left amygdala and right ventrolateral prefrontal cortex (vlPFC) activity during passive viewing of negative emotional images; greater dorsolateral PFC (dlPFC) activity during response inhibition to negative emotional cues; lower functional connectivity between the amygdala and vlPFC during emotional regulation; and greater ventral striatal and left vlPFC activity during uncertain reward anticipation. However, these studies often suffered from small sample sizes and limited exploration of different impulsivity subscales or a transdiagnostic approach. Furthermore, overlapping neural correlates with anhedonia, affective, and anxiety symptoms necessitate a design that differentiates these distinct constructs. Previous research has identified neural markers predictive of future affective symptoms in adolescents and future changes in anhedonia in young adults. However, to the researchers' knowledge, no prior studies have attempted to identify neural marker predictors of future impulsivity.

One hundred and fourteen young adults (ages 18–25) participated, including 47 healthy controls and 67 treatment-seeking individuals. Participants underwent a facial emotion processing task during fMRI scanning. Impulsivity was measured using the UPPS-P Impulsive Behavior Scale, with subscales for negative and positive urgency, lack of premeditation, lack of perseverance, and sensation seeking. Anhedonia was assessed using the Anhedonic Depression subscale of the MASQ-AD. Depression, anxiety, and mania/hypomania were assessed using the HAM-D, HAM-A, and YMRS, respectively. Elastic net penalized least squares regression was used for variable selection to identify relationships between neural activity (amygdala, vlPFC, mPFC) and symptom severity. Linear robust regression was used to test the significance of these relationships, controlling for demographic variables. Functional connectivity between the amygdala and other brain regions was examined using generalized psychophysiological interaction (gPPI). In a subsample (n=30), participants were reassessed at 6 months post-scan to predict future impulsivity worsening. Sensitivity analyses were conducted to examine the potential influence of bipolar disorder, diagnoses (MDD, GAD, ADHD), and medication status.

At baseline, impulsivity, particularly negative urgency and lack of perseverance, was significantly associated with greater left amygdala activity to facial fear (β = 0.82, *p* = 0.003; β = 0.68, *p* = 0.004, respectively) and lower amygdala-medial PFC functional connectivity to facial fear. Left vlPFC activity to facial anger was inversely associated with mania/hypomania (β = −2.08, *p* = 0.018). Importantly, amygdala activity to facial sadness predicted impulsivity severity 6 months later (β = 0.50, *p* = 0.017). No significant relationships were found between neural activity and 6-month anhedonia, affective, or anxiety symptoms. Sensitivity analyses, excluding participants with bipolar disorder or those taking medication, generally supported the primary findings regarding the relationship between amygdala activity and impulsivity.

The study's findings demonstrate a specific neural substrate for impulsivity, distinguishing it from other co-occurring symptoms. The association between amygdala activity and impulsivity, particularly negative urgency and lack of perseverance, suggests a key role for emotion processing in impulsivity. The predictive power of amygdala activity to facial sadness for future impulsivity highlights a potential neurobiological marker for identifying individuals at risk for worsening impulsivity. These findings provide novel targets for interventions aimed at reducing impulsivity and preventing the development of future mental health problems. The specificity of the findings for impulsivity, even when controlling for other symptoms, strengthens the conclusion that the observed neural patterns are not merely reflections of general psychopathology but rather a specific neural signature associated with impulsivity.

This study identified a specific neural substrate for impulsivity in young adults, characterized by increased amygdala activity and reduced amygdala-medial PFC connectivity. Amygdala activity to facial sadness predicted future impulsivity. These findings offer valuable insights into the neurobiology of impulsivity and suggest potential targets for interventions to prevent or mitigate its development and related mental health problems. Future research could explore the effectiveness of interventions targeting these neural circuits to reduce impulsivity and improve mental health outcomes in young adults. Further longitudinal studies with larger samples are needed to replicate these findings and investigate the long-term predictive validity of these neural markers.

The study's cross-sectional design limits inferences about causality. The sample, while large, might not fully generalize to all young adult populations. The reliance on self-report measures for some aspects of impulsivity introduces potential bias. Future studies should address these limitations to strengthen the generalizability and causal inferences of the results. The impact of specific medications on the observed neural patterns requires further investigation given that this was not directly examined.