Mandali Alekhya, Chakravarthy V Srinivasa
Computational Neuroscience Lab, Department of Biotechnology, Indian Institute of Technology Madras Chennai, India.
Front Hum Neurosci. 2016 Sep 12;10:450. doi: 10.3389/fnhum.2016.00450. eCollection 2016.
Everyday, we encounter situations where available choices are nearly equally rewarding (high conflict) calling for some tough decision making. Experimental recordings showed that the activity of Sub Thalamic Nucleus (STN) increases during such situations providing the extra time needed to make the right decision, teasing apart the most rewarding choice from the runner up closely trailing behind. This prolonged deliberation necessary for decision making under high conflict was absent in Parkinson's disease (PD) patients who underwent Deep Brain Stimulation (DBS) surgery of STN. In an attempt to understand the underlying cause of such adverse response, we built a 2D spiking network model (50 × 50 lattice) of Basal ganglia incorporating the key nuclei. Using the model we studied the Probabilistic learning task (PLT) in untreated, treated (L-Dopa and Dopamine Agonist) and STN-DBS PD conditions. Based on the experimental observation that dopaminergic activity is analogous to temporal difference (TD) and induces cortico-striatal plasticity, we introduced learning in the cortico-striatal weights. The results show that healthy and untreated conditions of PD model were able to more or less equally select (avoid) the rewarding (punitive) choice, a behavior that was absent in treated PD condition. The time taken to select a choice in high conflict trials was high in normal condition, which is in agreement with experimental results. The treated PD (Dopamine Agonist) patients made impulsive decisions (small reaction time) which in turn led to poor performance. The underlying cause of the observed impulsivity in DBS patients was studied in the model by (1) varying the electrode position within STN, (2) causing antidromic activation of GPe neurons. The effect of electrode position on reaction time was analyzed by studying the activity of STN neurons where, a decrease in STN neural activity was observed for certain electrode positions. We also observed that a higher antidromic activation of GPe neurons does not impact the learning ability but decreases reaction time as reported in DBS patients. These results suggest a probable role of electrode and antidromic activation in modulating the STN activity and eventually affecting the patient's performance on PLT.
每天，我们都会遇到一些情况，其中可获得的选择几乎同样有益（高冲突），这就需要做出一些艰难的决策。实验记录表明，在这种情况下，丘脑底核（STN）的活动会增加，从而提供做出正确决策所需的额外时间，将最有益的选择与紧随其后的次优选择区分开来。在接受STN深部脑刺激（DBS）手术的帕金森病（PD）患者中，在高冲突情况下进行决策所需的这种延长的思考过程并不存在。为了试图理解这种不良反应的潜在原因，我们构建了一个包含关键核团的基底神经节二维脉冲网络模型（50×50网格）。我们使用该模型研究了未经治疗、经治疗（左旋多巴和多巴胺激动剂）以及STN-DBS的PD患者的概率学习任务（PLT）。基于多巴胺能活动类似于时间差（TD）并诱导皮质-纹状体可塑性的实验观察结果，我们在皮质-纹状体权重中引入了学习。结果表明，PD模型的健康和未经治疗状态能够或多或少平等地选择（避免）有益（惩罚性）选择，而在经治疗的PD状态中则不存在这种行为。在正常情况下，在高冲突试验中做出选择所花费的时间较长，这与实验结果一致。经治疗的PD（多巴胺激动剂）患者会做出冲动决策（反应时间短），这反过来又导致表现不佳。通过以下方式在模型中研究了DBS患者中观察到的冲动行为的潜在原因：（1）改变STN内的电极位置，（2）引起苍白球外部（GPe）神经元的逆向激活。通过研究STN神经元的活动分析了电极位置对反应时间的影响，在某些电极位置观察到STN神经活动减少。我们还观察到，如DBS患者中所报道的那样，GPe神经元较高的逆向激活不会影响学习能力，但会缩短反应时间。这些结果表明电极和逆向激活在调节STN活动并最终影响患者在PLT上的表现方面可能发挥的作用。
