角膜电刺激对糖尿病大鼠前部缺血性视神经病变模型的影响

观察并评估角膜电刺激对糖尿病大鼠前部缺血性视神经病变（AION）模型的影响。方法：实验 研究。健康雄性Sparague-Dawley大鼠40只，随机分组后抽出8只作为正常大鼠组。余下32只先予 以链脲佐菌素腹腔注射建立糖尿病大鼠模型，将造模成功的大鼠随机抽出8只作为糖尿病组，余下 24只糖尿病大鼠采用孟加拉玫瑰红联合532 nm激光方法建立AION大鼠模型。将24只造模成功的 AION大鼠随机分成3组，每组8只，分别为AION模型组，不予任何处理；电刺激组，予以角膜电刺 激（刺激参数为：电流1 mA，频率20 Hz，波宽1 ms/phase，刺激时间1 h，隔日1次，刺激2周）；假电 刺激组，电极安放位置与电刺激组相同，仅不接通电源。2周后5组大鼠进行眼底照相、光学相干断 层扫描和视觉诱发电位，然后处死，行视网膜及视神经冰冻切片，苏木精伊红染色观察。数据采用 单因素方差分析和LSD-t检验进行分析。结果：正常大鼠组视盘上半部视网膜厚度为（211±13）μm， 糖尿病大鼠组为（206±16）μm，AION模型组为（240±54）μm，假电刺激组为（216±11）μm，电刺 激组为（198±4）μm，5组视盘上半部视网膜厚度差异有统计学意义（F=2.854，P=0.038）。其中AION 模型组视盘上半部视网膜厚度高于正常组、糖尿病组、电刺激组，差异均有统计学意义（P<0.05）； 正常组与糖尿病组差异无统计学意义，AION模型组与假电刺激组未见明显差异。视觉诱发电位示 AION模型组N1潜伏期较电刺激组延长，差异有统计学意义（t=4.1，P<0.001）；AION模型组P1潜伏 期较正常组、糖尿病组、假电刺激组、电刺激组延长，差异均有统计学意义（t=4.1、2.5、2.6、3.2， P<0.05）；电刺激组N1-P1波幅大于假电刺激组，差异有统计学意义（t=4.0，P<0.001）。结论：角膜电 刺激能促进糖尿病大鼠前部缺血性视神经病变模型肿胀的视盘变薄，加速视盘水肿的消退，同时在 一定程度上改善视功能。     

探讨基于近红外脑成像技术的阈下抑郁情志刺激反应机制研究可行性

近红外脑功能成像技术是近几年发展起来用于动态检测脑功能的方法,能够很好地反映抑郁人群认知活动期间大脑有氧代谢的变化,为阈下抑郁研究提供了一个新思路。本研究通过文献综述,结合中医情志理论,在过往研究的基础上基于近红外脑功能成像技术探讨中医情志刺激对阈下抑郁的反应机制,为后期研究提供理论与实践可行性的依据。     

Contribution of transcranial magnetic stimulation in restless legs syndrome: pathophysiological insights and therapeutical approaches

Transcranial magnetic stimulation (TMS) may offer a reliable means to characterize significant pathophysiologic and neurochemical aspects of restless legs syndrome (RLS). Namely, TMS has revealed specific patterns of changes in cortical excitability and plasticity, in particular dysfunctional inhibitory mechanisms and sensorimotor integration, which are thought to be part of the pathophysiological mechanisms of RLS rather than reflect a non-specific consequence of sleep architecture alteration.If delivered repetitively, TMS is able to transiently modulate the neural activity of the stimulated and connected areas. Some studies have begun to therapeutically use repetitive TMS (rTMS) to improve sensory and motor disturbances in RLS. High-frequency rTMS applied over the primary motor cortex or the supplementary motor cortex, as well as low-frequency rTMS over the primary somatosensory cortex, seem to have transient beneficial effects. However, further studies with larger patient samples, repeated sessions, an optimized rTMS setup, and clinical follow-up are needed in order to corroborate preliminary results.Thus, we performed a systematic search of all the studies that have used TMS and rTMS techniques in patients with RLS.     

Localization of motor and verbal fluency effects in subthalamic DBS for Parkinson's disease

IntroductionSubthalamic nucleus deep brain stimulation (STN DBS) improves cardinal motor symptoms of Parkinson's disease (PD) but can worsen verbal fluency (VF). An optimal site of stimulation for overall motor improvement has been previously identified using an atlas-independent, fully individualized, field-modeling approach. This study examines if cardinal motor components (bradykinesia, tremor, and rigidity) share this identified optimal improvement site and if there is co-localization with a site that worsens VF.MethodsAn atlas-independent, field-modeling approach was used to identify sites of maximal STN DBS effect on overall and cardinal motor symptoms and VF in 60 patients. Anatomic coordinates were referenced to the STN midpoint. Symptom severity was assessed with the MDS-UPDRS part III and established VF scales.ResultsSites for improved bradykinesia and rigidity co-localized with each other and the overall part III site (0.09 mm lateral, 0.93 mm posterior, 1.75 mm dorsal). The optimal site for tremor was posterior to this site (0.10 mm lateral, 1.40 mm posterior, 1.93 mm dorsal). Semantic and phonemic VF sites were indistinguishable and co-localized medial to the motor sites (0.32 mm medial, 1.18 mm posterior, 1.74 mm dorsal).ConclusionThis study identifies statistically distinct, maximally effective stimulation sites for tremor improvement, VF worsening, and overall and other cardinal motor improvements in STN DBS. Current electrode sizes and voltage settings stimulate all of these sites simultaneously. However, future targeted lead placement and focused directional stimulation may avoid VF worsening while maintaining motor improvements in STN DBS.     

Dry eye signs and symptoms in aromatase inhibitor treatment and the relationship with pain

PurposeAromatase inhibitors (AIs) limit the synthesis of oestrogen in peripheral tissues thus lowering levels of oestrogen. The primary aim was to evaluate whether women treated with AIs have altered dry eye symptoms and signs. A sub-aim was to investigate whether symptoms of dry eye in postmenopausal women were associated with symptoms of non-eye pain, ocular pain and self-rated pain perception.MethodsThis cross-sectional, observational, single visit study recruited 56 postmenopausal women (mean age 64.1 + 7.9 years) and 52 undergoing AI treatment (mean age 66.6 + 9.0). Ocular symptoms (OSDI, MGD14) and pain questionnaires (PSQ, OPAS) were administered and signs of dry eye and meibomian gland dysfunction were evaluated.ResultsAlmost half of each group reported dry eye symptoms, defined as OSDI>12 (48% control, 46% AI). The PSQ score was significantly higher in the AI group (p = 0.04). Neither frequency or severity of dry eye (or MGD) symptoms scores were significantly different between groups. In the AI group, meibomian gland expressibility score was worse (p = 0.003); there were no differences in any other signs. Higher OSDI scores were associated with higher OPAS eye-pain scores (r = 0.49, p < 0.001), but not OPAS non-eye pain (r = 0.09, p = 0.35). Pain perception (PSQ) showed a moderate positive association with OPAS eye-pain (r = 0.30, p = 0.003).ConclusionsIn this study elevated ocular symptoms were observed in both the AI treated and the untreated groups, with no difference between the groups. Women undergoing AI treatment for early stage breast cancer had worse meibum expressibility score and increased pain perception compared to an untreated group of women.     

Simulation of transcranial magnetic stimulation in head model with morphologically-realistic cortical neurons

BackgroundTranscranial magnetic stimulation (TMS) enables non-invasive modulation of brain activity with both clinical and research applications, but fundamental questions remain about the neural types and elements TMS activates and how stimulation parameters affect the neural response.ObjectiveTo develop a multi-scale computational model to quantify the effect of TMS parameters on the direct response of individual neurons.MethodsWe integrated morphologically-realistic neuronal models with TMS-induced electric fields computed in a finite element model of a human head to quantify the cortical response to TMS with several combinations of pulse waveforms and current directions.ResultsTMS activated with lowest intensity intracortical axonal terminations in the superficial gyral crown and lip regions. Layer 5 pyramidal cells had the lowest thresholds, but layer 2/3 pyramidal cells and inhibitory basket cells were also activated at most intensities. Direct activation of layers 1 and 6 was unlikely. Neural activation was largely driven by the field magnitude, rather than the field component normal to the cortical surface. Varying the induced current direction caused a waveform-dependent shift in the activation site and provided a potential mechanism for experimentally observed differences in thresholds and latencies of muscle responses.ConclusionsThis biophysically-based simulation provides a novel method to elucidate mechanisms and inform parameter selection of TMS and other cortical stimulation modalities. It also serves as a foundation for more detailed network models of the response to TMS, which may include endogenous activity, synaptic connectivity, inputs from intrinsic and extrinsic axonal projections, and corticofugal axons in white matter.