Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
J Neurosci. 2023 Jan 4;43(1):173-182. doi: 10.1523/JNEUROSCI.1237-22.2022. Epub 2022 Nov 17.
Heroin addiction imposes a devastating toll on society, with little known about its neurobiology. Excessive salience attribution to drug over nondrug cues/reinforcers, with concomitant inhibitory control decreases, are common mechanisms underlying drug addiction. Although inhibitory control alterations generally culminate in prefrontal cortex (PFC) hypoactivations across drugs of abuse, patterns in individuals with heroin addiction (iHUDs) remain unknown. We used a stop-signal fMRI task designed to meet recent consensus guidelines in mapping inhibitory control in 41 iHUDs and 24 age- and sex-matched healthy controls (HCs). Despite group similarities in the stop-signal response time (SSRT; the classic inhibitory control measure), compared with HCs, iHUDs exhibited impaired target detection sensitivity (proportion of hits in go vs false alarms in stop trials; = 0.003). Additionally, iHUDs exhibited lower right anterior PFC (aPFC) and dorsolateral PFC (dlPFC) activity during successful versus failed stops (the hallmark inhibitory control contrast). Lower left dlPFC/supplementary motor area (SMA) activity was associated with slower SSRT specifically in iHUDs and lower left aPFC activity with worse target sensitivity across all participants ( < 0.05 corrected). Importantly, in iHUDs, lower left SMA and aPFC activity during inhibitory control was associated with shorter time since last use and higher severity of dependence, respectively ( < 0.05 corrected). Together, results revealed lower perceptual sensitivity and hypoactivations during inhibitory control in cognitive control regions (e.g., aPFC, dlPFC, SMA) as associated with task performance and heroin use severity measures in iHUDs. Such neurobehavioral inhibitory control deficits may contribute to self-control lapses in heroin addiction, constituting targets for prevention and intervention efforts to enhance recovery. Heroin addiction continues its deadly impact, with little known about the neurobiology of this disorder. Although behavioral and prefrontal cortical impairments in inhibitory control characterize addiction across drugs of abuse, these patterns remain underexplored in heroin addiction. Here, we illustrate a significant behavioral impairment in target discrimination in individuals with heroin addiction compared with matched healthy controls. We further show lower engagement during inhibitory control in the anterior and dorsolateral prefrontal cortex (key regions that regulate cognitive control) as associated with slower stopping, worse discrimination, and heroin use measures. Mapping the neurobiology of inhibitory control in heroin addiction for the first time, we identify potential treatment targets inclusive of prefrontal cortex-mediated cognitive control amenable for neuromodulation en route to recovery.
海洛因成瘾给社会带来了毁灭性的影响，但人们对其神经生物学知之甚少。药物与非药物线索/强化物之间的过度显著归因，伴随着随之而来的抑制控制减少，是药物成瘾的常见机制。尽管抑制控制的改变通常最终导致滥用药物的前额叶皮层（PFC）活动减少，但在海洛因成瘾者（iHUDs）中，模式仍然未知。我们使用了停止信号 fMRI 任务，旨在根据最近的共识指南，对 41 名 iHUDs 和 24 名年龄和性别匹配的健康对照者（HCs）的抑制控制进行映射。尽管 iHUDs 和 HCs 在停止信号反应时间（SSRT；经典的抑制控制测量）上存在相似之处，但与 HCs 相比，iHUDs 表现出目标检测敏感性受损（GO 中的命中比例与停止试验中的错误警报；= 0.003）。此外，在成功和失败的停止之间，iHUDs 的右侧前前额叶皮层（aPFC）和背外侧前额叶皮层（dlPFC）活动较低（抑制控制的标志性对比）。较低的左侧 dlPFC/辅助运动区（SMA）活动与 iHUDs 中较慢的 SSRT 特异性相关，而较低的左侧 aPFC 活动与所有参与者的较差目标敏感性相关（<0.05 校正）。重要的是，在 iHUDs 中，抑制控制期间较低的左侧 SMA 和 aPFC 活动与最后一次使用时间较短和依赖性严重程度较高分别相关（<0.05 校正）。总之，结果表明，在认知控制区域（例如 aPFC、dlPFC、SMA）的抑制控制期间，较低的感知敏感性和低激活与 iHUDs 的任务表现和海洛因使用严重程度测量相关。这种神经行为抑制控制缺陷可能导致海洛因成瘾中的自我控制失误，构成预防和干预措施的目标，以增强康复。海洛因成瘾仍在继续造成致命影响，但对这种疾病的神经生物学知之甚少。尽管抑制控制在各种滥用药物中的行为和前额叶皮质损伤特征，但这些模式在海洛因成瘾中仍未得到充分探索。在这里，我们与匹配的健康对照组相比，在海洛因成瘾者中观察到目标辨别能力的显著行为障碍。我们进一步表明，在抑制控制期间，前和背外侧前额叶皮层（调节认知控制的关键区域）的参与度较低，与较慢的停止、较差的辨别力和海洛因使用测量相关。这是首次在海洛因成瘾中映射抑制控制的神经生物学，我们确定了潜在的治疗靶点，包括前额叶皮层介导的认知控制，这些靶点可通过神经调节来实现康复。
