From learning to action: the integration of dorsal striatal input and output pathways in instrumental conditioning

Considerable evidence suggests that the learning and performance of instrumental actions depend on activity in basal ganglia circuitry; however, these two functions have generally been considered independently. Whereas research investigating the associative mechanisms underlying instrumental conditioning has identified critical cortical and limbic input pathways to the dorsal striatum, the performance of instrumental actions has largely been attributed to activity in the dorsal striatal output pathways, with direct and indirect pathway projection neurons mediating action initiation, perseveration and cessation. Here, we discuss evidence that the dorsal striatal input and basal ganglia output pathways mediate the learning and performance of instrumental actions, respectively, with the dorsal striatum functioning as a transition point. From this perspective, the issue of how multiple striatal inputs are integrated at the level of the dorsal striatum and converted into relatively restricted outputs becomes one of critical significance for understanding how learning is translated into action. So too does the question of how learning signals are modulated by recent experience. We propose that this occurs through recurrent corticostriatothalamic feedback circuits that serve to integrate performance signals by updating ongoing action‐related learning.     

Restoration of functional network state towards more physiological condition as the correlate of clinical effects of pallidal deep brain stimulation in dystonia

BackgroundDeep brain stimulation of the internal globus pallidus (GPi DBS) is an invasive therapeutic modality intended to retune abnormal central nervous system patterns and relieve the patient of dystonic or other motor symptoms.ObjectivesThe aim of the presented research was to determine the neuroanatomical signature of GPi DBS modulation and its association with the clinical outcome.MethodsThis open-label fixed-order study with cross-sectional validation against healthy controls analysed the resting-state functional MRI activity changes induced by GPi DBS in 18 dystonia patients of heterogeneous aetiology, focusing on both global (full brain) and local connectivity (local signal homogeneity).ResultsCompared to the switched-off state, the activation of GPi DBS led to the restoration of global subcortical connectivity patterns (in both putamina, diencephalon and brainstem) towards those of healthy controls, with positive direct correlation over large-scale cortico-basal ganglia-thalamo-cortical and cerebellar networks with the clinical improvement. Nonetheless, on average, GPi DBS also seemed to bring local connectivity both in the cortical and subcortical regions farther away from the state detected in healthy controls. Interestingly, its correlation with clinical outcome showed that in better DBS responders, local connectivity defied this effect and approached healthy controls.ConclusionsAll in all, the extent of restoration of both these main metrics of interest towards the levels found in healthy controls clearly correlated with the clinical improvement, indicating that the restoration of network state towards more physiological condition may be a precondition for successful GPi DBS outcome in dystonia.     

Subthalamic nucleus deep brain stimulation improves sleep in Parkinson's disease patients: a retrospective study and a meta-analysis

BackgroundMost Parkinson's patients suffered from sleep problems. There is increasing evidence that Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) has a positive effect on several sleep parameters, improving overall sleep quality in patients with PD. However, the results are controversial.MethodsWe performed a retrospective study and meta-analysis to assess the Parkinson's disease sleep scale (PDSS) in Parkinson's patients.ResultsWe reviewed our data of patients who underwent STN-DBS, and then extracted five other trials to perform a meta-analysis. The pooled results showed an advantage on post-operative PDSS in both our medical center and pooled results (MD = 20.41, 95% CI = [13.03, 27.79], I² = 61%, P < 0.001). There was a significant difference in Unified Parkinson's Disease Rating Scale (UPDRS)-Ⅲ score between pre and post-operation (MD = −12.59, 95% CI = [−14.70, −10.49], I² = 90%, P < 0.001). What's more, Parkinsonian medication was significantly lower in the post-operative groups after DBS (MD = −314.71, 95% CI = [−468.13, −161.28], I² = 53%, P < 0.001).ConclusionIn the retrospective study and meta-analysis of 6 trials, we found that DBS can significantly increase sleep quality. Furthermore, motor function improved and Parkinsonian medication was significantly decreased postoperatively. The sample size was enough and no further investigations would change the conclusion.     

Characteristics of globus pallidus internus local field potentials in generalized dystonia patients with TWNK mutation

ObjectiveWe focused on a rare gene mutation causing dystonia in two siblings who received globus pallidus internus deep brain stimulation (GPi-DBS). The aim was to characterize the relationship between neuronal activity patterns and clinical syndromes.MethodsWhole exome sequencing was applied to identify the TWNK (previous symbol C10orf2) mutation; Two siblings with TWNK mutation presented as generalized dystonia with rigidity and bradykinesia; four other sporadic generalized dystonia patients underwent GPi-DBS and local field potentials (LFPs) were recorded. Oscillatory activities were illustrated with power spectra and temporal dynamics measured by the Lempel-Ziv complexity (LZC).ResultsNormalized power spectra of GPi LFPs differed between patients with TWNK mutation and dystonia over the low beta bands. Patients with TWNK mutation had higher low beta power (15–27 Hz, unpaired t-test, corrected P < 0.0022) and lower LZC (15–27 Hz, unpaired t-test, P < 0.01) than other patients with generalized dystonia. On the other hand, the TWNK mutation patients showed decreased low frequency and beta oscillation in the GPi after DBS, as well as improved movement performance.ConclusionThe LFPs were different in TWNK mutation dystonia siblings than other patients with generalized dystonia, which indicate the abnormal LFPs were related to symptoms rather than specific disease. In addition, the inhibited effect on oscillations also provided a potential evidence for DBS treatment on rare movement disorders.SignificanceThis study could potentially aid in the future development of adaptive DBS via rare disease LFPs comparison.     

Toward sophisticated basal ganglia neuromodulation: Review on basal ganglia deep brain stimulation

This review presents state-of-the-art knowledge about the roles of the basal ganglia (BG) in action-selection, cognition, and motivation, and how this knowledge has been used to improve deep brain stimulation (DBS) treatment of neurological and psychiatric disorders. Such pathological conditions include Parkinson's disease, Huntington's disease, Tourette syndrome, depression, and obsessive-compulsive disorder. The first section presents evidence supporting current hypotheses of how the cortico-BG circuitry works to select motor and emotional actions, and how defects in this circuitry can cause symptoms of the BG diseases. Emphasis is given to the role of striatal dopamine on motor performance, motivated behaviors and learning of procedural memories. Next, the use of cutting-edge electrochemical techniques in animal and human studies of BG functioning under normal and disease conditions is discussed. Finally, functional neuroimaging studies are reviewed; these works have shown the relationship between cortico-BG structures activated during DBS and improvement of disease symptoms.     

半夏厚朴汤治疗梅核气随机对照试验的Meta分析

目的:系统评价半夏厚朴汤治疗梅核气的临床疗效。方法:计算机检索CNKI中国知网(总库)(1979-2013)、维普期刊资源整合服务平台(1989-2013)、美国图书馆Pub Med/MEDLINE相关文献。根据Jadad量表对纳入文献进行质量评价。采用Cochrane协作网提供的Rev Man 5.2.0分析软件进行Meta分析。结果:共纳入6项临床随机对照研究,包括649例梅核气患者。Meta分析结果显示,半夏厚朴汤与西药比较治疗梅核气的总体疗效RR=1.15,95%CI(1.08,1.23);半夏厚朴汤合西医治疗与单纯西医治疗梅核气的总体疗效RR=1.43,95%CI(1.19,1.73)。结论:当前的临床证据显示,单用半夏厚朴汤或联用西医治疗梅核气疗效均优于单用西医治疗者,且无明显副作用。由于纳入研究样本量小且质量较低,尚需开展高质量、多中心、大样本的临床随机双盲对照试验加以证实。