- 作者列表："Ersche KD","Meng C","Ziauddeen H","Stochl J","Williams GB","Bullmore ET","Robbins TW
:Regular drug use can lead to addiction, but not everyone who takes drugs makes this transition. How exactly drugs of abuse interact with individual vulnerability is not fully understood, nor is it clear how individuals defy the risks associated with drugs or addiction vulnerability. We used resting-state functional MRI (fMRI) in 162 participants to characterize risk- and resilience-related changes in corticostriatal functional circuits in individuals exposed to stimulant drugs both with and without clinically diagnosed drug addiction, siblings of addicted individuals, and control volunteers. The likelihood of developing addiction, whether due to familial vulnerability or drug use, was associated with significant hypoconnectivity in orbitofrontal and ventromedial prefrontal cortical-striatal circuits-pathways critically implicated in goal-directed decision-making. By contrast, resilience against a diagnosis of substance use disorder was associated with hyperconnectivity in two networks involving 1) the lateral prefrontal cortex and medial caudate nucleus and 2) the supplementary motor area, superior medial frontal cortex, and putamen-brain circuits respectively implicated in top-down inhibitory control and the regulation of habits. These findings point toward a predisposing vulnerability in the causation of addiction, related to impaired goal-directed actions, as well as countervailing resilience systems implicated in behavioral regulation, and may inform novel strategies for therapeutic and preventative interventions.
: 经常吸毒会导致成瘾，但不是每个吸毒的人都有这种转变。滥用药物究竟如何与个体脆弱性相互作用尚不完全清楚，也不清楚个体如何对抗与药物或成瘾脆弱性相关的风险。我们使用静息态功能 MRI (fMRI) 在 162 名参与者中，表征有或无临床诊断的药物成瘾、成瘾个体的兄弟姐妹和对照志愿者暴露于刺激性药物的个体的皮质纹状体功能环路的风险和恢复力相关变化。成瘾的可能性，无论是由于家族脆弱性还是吸毒,与眶额叶和腹内侧前额叶皮层-纹状体环路的显著低连接相关-通路与目标导向决策密切相关。相比之下，针对物质使用障碍诊断的复原力与两个网络中的超连接性相关，涉及 1) 外侧前额叶皮层和内侧尾状核，2) 补充运动区,上内侧额叶皮质和壳核-脑环路分别涉及自上而下的抑制控制和习惯的调节。这些发现指出了成瘾因果关系中的易感脆弱性，与受损的目标导向行动相关，以及与行为调节相关的对抗复原力系统,并可能告知治疗和预防干预的新策略。
METHODS::In recent years, transcranial electrical stimulation (tES) has been used to improve cognitive and perceptual abilities and to boost learning. In the visual domain, transcranial random noise stimulation (tRNS), a type of tES in which electric current is randomly alternating in between two electrodes at high frequency, has shown potential in inducing long lasting perceptual improvements when coupled with tasks such as contrast detection. However, its cortical mechanisms and online effects have not been fully understood yet, and it is still unclear whether these long-term improvements are due to early-stage perceptual enhancements of contrast sensitivity or later stage mechanisms such as learning consolidation. Here we tested tRNS effects on multiple spatial frequencies and orientation, showing that tRNS enhances detection of a low contrast Gabor, but only for oblique orientation and high spatial frequency (12 cycles per degree of visual angle). No improvement was observed for low contrast and vertical stimuli. These results indicate that tRNS can enhance contrast sensitivity already after one training session, however this early onset is dependent on characteristics of the stimulus such as spatial frequency and orientation. In particular, the shallow depth of tRNS is likely to affect superficial layers of the visual cortex where neurons have higher preferred spatial frequencies than cells in further layers, while the lack of effect on vertical stimuli might reflect the optimization of the visual system to see cardinally oriented low contrast stimuli, leaving little room for short-term improvement. Taken together, these results suggest that online tRNS effects on visual perception are the result of a complex interaction between stimulus intensity and cortical anatomy, consistent with previous literature on brain stimulation.
METHODS:OBJECTIVE:There is growing interest in treating diseases by electrical stimulation and block of peripheral autonomic nerves, but a paucity of studies on excitation and block of small diameter autonomic axons. We conducted in vivo quantification of the strength-duration properties, activity-dependent slowing (ADS), and responses to kilohertz frequency (KHF) signals for the rat vagus nerve (VN). APPROACH:We conducted acute in vivo experiments in urethane-anesthetised rats. We placed two cuff electrodes on the left cervical VN and one cuff electrode on the anterior subdiaphragmatic VN. The rostral cervical cuff was used to deliver pulses to quantify recruitment and ADS. The caudal cervical cuff was used to deliver KHF signals. The subdiaphragmatic cuff was used to record compound action potentials (CAPs). MAIN RESULTS:We quantified the input-output recruitment and strength-duration curves. Fits to the data using standard strength-duration equations were qualitatively similar, but the resulting chronaxie and rheobase estimates varied substantially. We measured larger thresholds for the slowest fibres (0.5 to 1 m/s), especially at shorter pulse widths. Using a novel cross-correlation CAP-based analysis, we measured ADS of ~2.3% after 3 min of 2 Hz stimulation, which is comparable to ADS reported for sympathetic efferents in somatic nerves, but much smaller than ADS in cutaneous nociceptors. We found greater ADS with higher stimulation frequency and non-monotonic changes in CV in select cases. We found monotonically increasing block thresholds across frequencies from 10 to 80 kHz for both fast and slow fibres. Further, following 25 s of KHF signal, neural conduction could require tens of seconds to recover. SIGNIFICANCE:The quantification of mammalian autonomic nerve responses to conventional and KHF signals provides essential information for development of peripheral nerve stimulation therapies and for understanding their mechanisms of action.
METHODS:BACKGROUND:Early accounts of forced thought were reported at the onset of a focal seizure, and characterized as vague, repetitive, and involuntary intellectual auras distinct from perceptual or psychic hallucinations or illusions. Here, we examine the neural underpinnings involved in conceptual thought by presenting a series of 3 patients with epilepsy reporting intrusive thoughts during electrical stimulation of the left lateral prefrontal cortex (PFC) during invasive surgical evaluation. We illustrate the widespread networks involved through two independent brain imaging modalities: resting state functional magnetic resonance imaging (fMRI) (rs-fMRI) and task-based meta-analytic connectivity modeling (MACM). METHODS:We report the clinical and stimulation characteristics of three patients with left hemispheric language dominance who demonstrate forced thought with functional mapping. To examine the brain networks underlying this phenomenon, we used the regions of interest (ROI) centered at the active electrode pairs. We modeled functional networks using two approaches: (1) rs-fMRI functional connectivity analysis, representing 81 healthy controls and (2) meta-analytic connectivity modeling (MACM), representing 8260 healthy subjects. We also determined the overlapping regions between these three subjects' rs-fMRI and MACM networks through a conjunction analysis. RESULTS:We identified that left PFC was associated with a large-scale functional network including frontal, temporal, and parietal regions, a network that has been associated with multiple cognitive functions including semantics, speech, attention, working memory, and explicit memory. CONCLUSIONS:We illustrate the neural networks involved in conceptual thought through a unique patient population and argue that PFC supports this function through activation of a widespread network.