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<p>Mania/hypomania is pathognomonic of bipolar disorder (BD), yet early identification remains challenging. Impulsivity is a key feature of mania/hypomania and of externalizing disorders that may predispose to BD, but neural markers of impulsivity-related risk remain unknown. This study aimed to identify reward expectancy (RE)-related neural correlates of impulsivity facets, test moderation by current affective/anxiety symptoms, and determine whether such markers differentiate BD and/or externalizing disorders from low impulsivity individuals. Two independent BD-risk samples aged 18–30 years, including individuals with prior externalizing disorder diagnoses but not BD, were recruited; a euthymic BD group was also recruited. Impulsivity facets were assessed via Behavioral Activation System (BAS) and UPPS-P scales. Whole-brain regressions identified neural correlates of impulsivity facets during RE. Linear models tested replication and current affective/anxiety symptom moderation. ANCOVA compared neural activity among BD, externalizing, and non-BD/externalizing impulsivity tertile groups. Whole-brain regressions revealed a positive association between BAS Fun Seeking and pre-supplementary motor area (pre-SMA) activity (<i>p</i><sub>FWE</sub> = 0.003, <i>k</i> = 167), which replicated when depressive symptoms were covaried (discovery: <i>β</i> = 2.73, <i>p</i> &lt; 0.001; replication: <i>β</i> = 0.88, <i>p</i> = 0.036; combined: <i>β</i> = 1.49, <i>p</i> &lt; 0.001). A significant pre-SMA × depression interaction (<i>β</i> = –0.08, <i>p</i> = 0.037) indicated depressive symptoms attenuated the pre-SMA-Fun Seeking association. Group comparisons revealed greater pre-SMA activity in high-Fun Seeking (<i>p</i> &lt; 0.001) and externalizing disorder groups (<i>p</i> = 0.039) versus low-Fun Seeking, with similar trends observed in BD once individuals taking medications, particularly benzodiazepines (<i>p</i> = 0.012), were excluded. Pre-SMA hyperactivity during RE is a robust neural correlate of BAS Fun Seeking, moderated by depression severity. This pattern represents a trait-linked neural marker of impulsivity associated with vulnerability to BD and externalizing disorders, informing early risk identification and intervention.</p>

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Elevated pre-supplementary motor area activity during reward expectancy: An impulsivity-related neural marker of vulnerability to bipolar and externalizing disorders

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月19日

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  • Robert Raeder,
  • Manan Arora,
  • Michele Bertocci,
  • Henry W. Chase,
  • Alexander S. Skeba,
  • Genna Bebko,
  • Haris A. Aslam,
  • Simona Graur,
  • Osasumwen Benjamin,
  • Yiming Wang,
  • Richelle Stiffler,
  • Mary L. Phillips

摘要

Mania/hypomania is pathognomonic of bipolar disorder (BD), yet early identification remains challenging. Impulsivity is a key feature of mania/hypomania and of externalizing disorders that may predispose to BD, but neural markers of impulsivity-related risk remain unknown. This study aimed to identify reward expectancy (RE)-related neural correlates of impulsivity facets, test moderation by current affective/anxiety symptoms, and determine whether such markers differentiate BD and/or externalizing disorders from low impulsivity individuals. Two independent BD-risk samples aged 18–30 years, including individuals with prior externalizing disorder diagnoses but not BD, were recruited; a euthymic BD group was also recruited. Impulsivity facets were assessed via Behavioral Activation System (BAS) and UPPS-P scales. Whole-brain regressions identified neural correlates of impulsivity facets during RE. Linear models tested replication and current affective/anxiety symptom moderation. ANCOVA compared neural activity among BD, externalizing, and non-BD/externalizing impulsivity tertile groups. Whole-brain regressions revealed a positive association between BAS Fun Seeking and pre-supplementary motor area (pre-SMA) activity (pFWE = 0.003, k = 167), which replicated when depressive symptoms were covaried (discovery: β = 2.73, p < 0.001; replication: β = 0.88, p = 0.036; combined: β = 1.49, p < 0.001). A significant pre-SMA × depression interaction (β = –0.08, p = 0.037) indicated depressive symptoms attenuated the pre-SMA-Fun Seeking association. Group comparisons revealed greater pre-SMA activity in high-Fun Seeking (p < 0.001) and externalizing disorder groups (p = 0.039) versus low-Fun Seeking, with similar trends observed in BD once individuals taking medications, particularly benzodiazepines (p = 0.012), were excluded. Pre-SMA hyperactivity during RE is a robust neural correlate of BAS Fun Seeking, moderated by depression severity. This pattern represents a trait-linked neural marker of impulsivity associated with vulnerability to BD and externalizing disorders, informing early risk identification and intervention.