Walia Pushpinder, Ghosh Abhishek, Singh Shubhmohan, Dutta Anirban
Neuroengineering and Informatics for Rehabilitation Laboratory, University at Buffalo, Buffalo, NY 14228, USA.
Postgraduate Institute of Medical Education & Research, Chandigarh 700020, India.
Brain Sci. 2022 Mar 26;12(4):445. doi: 10.3390/brainsci12040445.
Maladaptive neuroplasticity-related learned response in substance use disorder (SUD) can be ameliorated using noninvasive brain stimulation (NIBS); however, inter-individual variability needs to be addressed for clinical translation.
Our first objective was to develop a hypothesis for NIBS for learned response in SUD based on a competing neurobehavioral decision systems model. The next objective was to develop the theory by conducting a computational simulation of NIBS of the cortico-cerebello-thalamo-cortical (CCTC) loop in cannabis use disorder (CUD)-related dysfunctional "cue-reactivity"-a construct closely related to "craving"-that is a core symptom. Our third objective was to test the feasibility of a neuroimaging-guided rational NIBS approach in healthy humans.
"Cue-reactivity" can be measured using behavioral paradigms and portable neuroimaging, including functional near-infrared spectroscopy (fNIRS) and electroencephalogram (EEG) metrics of sensorimotor gating. Therefore, we conducted a computational simulation of NIBS, including transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) of the cerebellar cortex and deep cerebellar nuclei (DCN) of the CCTC loop for its postulated effects on fNIRS and EEG metrics. We also developed a rational neuroimaging-guided NIBS approach for the cerebellar lobule (VII) and prefrontal cortex based on a healthy human study.
Simulation of cerebellar tDCS induced gamma oscillations in the cerebral cortex, while transcranial temporal interference stimulation induced a gamma-to-beta frequency shift. A preliminary healthy human study (N = 10) found that 2 mA cerebellar tDCS evoked similar oxyhemoglobin (HbO) response in the range of 5 × 10 M across the cerebellum and PFC brain regions (α = 0.01); however, infra-slow (0.01-0.10 Hz) prefrontal cortex HbO-driven phase-amplitude-coupled (PAC; 4 Hz, ±2 mA (max)) cerebellar tACS evoked HbO levels in the range of 10 M that were statistically different (α = 0.01) across these brain regions.
Our healthy human study showed the feasibility of fNIRS of cerebellum and PFC and closed-loop fNIRS-driven ctACS at 4 Hz, which may facilitate cerebellar cognitive function via the frontoparietal network. Future work needs to combine fNIRS with EEG for multi-modal imaging for closed-loop NIBS during operant conditioning.
物质使用障碍（SUD）中与适应不良的神经可塑性相关的习得性反应可通过非侵入性脑刺激（NIBS）得到改善；然而，为实现临床转化，个体间差异问题仍需解决。
我们的首要目标是基于一个相互竞争的神经行为决策系统模型，为SUD中的习得性反应制定NIBS假设。接下来的目标是通过对大麻使用障碍（CUD）相关功能失调的“线索反应性”（一种与“渴望”密切相关的结构，是核心症状）进行皮质 - 小脑 - 丘脑 - 皮质（CCTC）环路的NIBS计算模拟来发展该理论。我们的第三个目标是在健康人类中测试神经影像引导的合理NIBS方法的可行性。
“线索反应性”可使用行为范式和便携式神经影像进行测量，包括感觉运动门控的功能近红外光谱（fNIRS）和脑电图（EEG）指标。因此，我们对NIBS进行了计算模拟，包括对CCTC环路的小脑皮质和小脑深部核团（DCN）进行经颅直流电刺激（tDCS）和经颅交流电刺激（tACS），以推测其对fNIRS和EEG指标的影响。我们还基于一项健康人类研究，为小脑小叶（VII）和前额叶皮质开发了一种合理的神经影像引导的NIBS方法。
小脑tDCS模拟在大脑皮质中诱发了伽马振荡，而经颅颞叶干扰刺激诱发了从伽马到贝塔的频率转变。一项初步的健康人类研究（N = 10）发现，2 mA的小脑tDCS在小脑和前额叶皮质脑区诱发了类似的氧合血红蛋白（HbO）反应，范围在5×10⁻⁶ M（α = 0.01）；然而，超慢（0.01 - 0.10 Hz）的前额叶皮质HbO驱动的相位 - 振幅耦合（PAC；4 Hz，±2 mA（最大值））小脑tACS在这些脑区诱发的HbO水平范围为10⁻⁶ M，在统计学上存在差异（α = 0.01）。
我们的健康人类研究表明，小脑和前额叶皮质的fNIRS以及4 Hz的闭环fNIRS驱动的ctACS具有可行性，这可能通过额顶叶网络促进小脑认知功能。未来的工作需要将fNIRS与EEG结合，用于操作性条件反射期间闭环NIBS的多模态成像。
