Acute Changes in Mood Induced by Subthalamic Deep Brain Stimulation in Parkinson Disease Are Modulated by Psychiatric Diagnosis

BackgroundDeep brain stimulation of the subthalamic nucleus (STN DBS) reduces Parkinson disease (PD) motor symptoms but has unexplained, variable effects on mood.ObjectiveThe study tested the hypothesis that pre-existing mood and/or anxiety disorders or increased symptom severity negatively affects mood response to STN DBS.MethodsThirty-eight PD participants with bilateral STN DBS and on PD medications were interviewed with Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID) and completed Beck Depression Inventory (BDI) and Spielberger State Anxiety Inventory (SSAI) self-reports. Subsequently, during OFF and optimal ON (clinical settings) STN DBS conditions and while off PD medications, motor function was assessed with the United Parkinson Disease Rating Scale (UPDRS, part III), and participants rated their mood with Visual Analogue Scales (VAS), and again completed SSAI. VAS mood variables included anxiety, apathy, valence and emotional arousal.ResultsSTN DBS improved UPDRS scores and mood. Unexpectedly, PD participants diagnosed with current anxiety or mood disorders experienced greater STN DBS-induced improvement in mood than those diagnosed with remitted disorders or who were deemed as having never met threshold criteria for diagnosis. BDI and SSAI scores did not modulate mood response to STN DBS, indicating that clinical categorical diagnosis better differentiates mood response to STN DBS than self-rated symptom severity. SCID diagnosis, BDI and SSAI scores did not modulate motor response to STN DBS.ConclusionsPD participants diagnosed with current mood or anxiety disorders are more sensitive to STN DBS-induced effects on mood, possibly indicating altered basal ganglia circuitry in this group.     

fMRI BOLD Signal Changes in Elite Swimmers While Viewing Videos of Personal Failure

Athletes who fail are susceptible to negative affect (NA) and impaired future performance. Functional magnetic resonance imaging (fMRI) studies have identified prefrontal, anterior cingulate, and limbic activations following negative mood provocation. Little is known about the neural correlates of negative self-reference (SR), especially in athletes. Even less is known about the neural correlates of the effects of cognitive intervention (CI) in modifying negative SR and NA in this population. In an fMRI study, 13 athletes watched a video of their own career-threatening defeat in two controlled blocks. Between fMRI blocks, they received a 20-min CI designed to assist in event reappraisal and planning for future performance. Relative increases post-CI were seen in premotor (BA6) and sensorimotor (BA4/1) cortices. Correlated with mood ratings, relatively higher pre-CI levels were seen in the ventromedial prefrontal cortex, the right dorsomedial prefrontal cortex (PFC; BA10), the right dorsolateral PFC (BA45), the anterior cingulate, and the right parahippocampus. CI may counteract the detrimental effects of NA and negative SR on premotor and motor activity.     

Subthalamic Nucleus Stimulation–Induced Local Field Potential Changes in Dystonia

Background

Subthalamic nucleus (STN) stimulation is an effective treatment for Parkinson's disease and induced local field potential (LFP) changes that have been linked with clinical improvement. STN stimulation has also been used in dystonia although the internal globus pallidus is the standard target where theta power has been suggested as a physiomarker for adaptive stimulation.

Objective

We aimed to explore if enhanced theta power was also present in STN and if stimulation-induced spectral changes that were previously reported for Parkinson's disease would occur in dystonia.

Methods

We recorded LFPs from 7 patients (12 hemispheres) with isolated craniocervical dystonia whose electrodes were placed such that inferior, middle, and superior contacts covered STN, zona incerta, and thalamus.

Results

We did not observe prominent theta power in STN at rest. STN stimulation induced similar spectral changes in dystonia as in Parkinson's disease, such as broadband power suppression, evoked resonant neural activity (ERNA), finely-tuned gamma oscillations, and an increase in aperiodic exponents in STN-LFPs. Both power suppression and ERNA localize to STN. Based on this, single-pulse STN stimulation elicits evoked neural activities with largest amplitudes in STN, which are relayed to the zona incerta and thalamus with changing characteristics as the distance from STN increases.

Conclusions

Our results show that STN stimulation–induced spectral changes are a nondisease-specific response to high-frequency stimulation, which can serve as placement markers for STN. This broadens the scope of STN stimulation and makes it an option for other disorders with excessive oscillatory peaks in STN. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Histopathological Changes Induced by Disturbance of Microcirculation in the Rat Brain

Abstract: Microcirculatory disturbance was induced in 8 rats after injecting micro-sphere latex (5 micron in diameter) from the right carotid artery.
Ultrastructural observations revealed that initial changes occurred in the vascular feet of astroglial cells the subsequent swelling of postsynapses.
Succeedlngly presynapses nerve cells also became atrophic but this was considered to be caused by astrocytic degeneration.
From these findings, it is speculated that the neuronai atrophy was secondary to the changes in the neuropil around the capillary caused by disturbance of the nutritional supply from the blood induced by micmcirculatory disturbance.
The above described findings seemed to have some similarity to those of nonspecific degeneration of the cortex observed in the brain, such as Alzheimer's disease.     

D-半乳糖老化小鼠神经元信号转导通路的改变以及APP63-73的作用

目的　观察D -半乳糖老化小鼠海马神经元神经生长因子(nerve growth factor, NGF)信号转导通路的改变以及APP63 -73的作用。方法　采用免疫组化染色法检测 D -半乳糖老化小鼠模型海马神经元 NGF、PI3′K、Akt和CREB的表达水平,并观察APP63 73的保护作用。结果　D- 半乳糖老化小鼠海马CA1区信号转导通路中相关蛋白表达水平明显减少,与对照组比较差异有显著性(P<0 .01),APP63- 73 组上述各种蛋白的表达结果与对照组相近。结论　D- 半乳糖老化小鼠海马神经元存在信号转导通路障碍,APP63 -73 可使之恢复正常水平并发挥神经营养和保护作用,提示其在治疗神经元退行性变中可能有应用前景。     

Apathy Induced by Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease: A Meta-Analysis

Apathy, the loss of motivation, is a common problem in Parkinson's disease (PD) and often observed following deep brain stimulation (DBS) of the subthalamic nucleus (STN). The aim of this meta-analysis was to determine the occurrence of apathy following STN DBS in literature. Relevant articles were searched in PubMed/Medline, SCOPUS, EMBASE, and Web of Sciences electronic databases. Studies were included if they reported apathy scores pre- and post-DBS or the cross-sectional difference between PD patients receiving STN DBS and patients receiving medication only. Thirty-three articles were included in the meta-analyses from 6,658 screened articles by two authors independently. A total of 1,286 patients were included with a mean age (±standard deviation [SD]) of 58.4 ± 8.5 years and a disease duration of 11.0 ± 5.8 years. The apathy score measured by means of the Apathy Evaluation Scale (AES), Starkstein Apathy Scale (SAS), and the Lille Apathy Rating Scale (LARS) was significantly higher after DBS than pre-operatively (g = 0.34, 95% confidence interval [CI] = 0.19–0.48, P < 0.001). An equal, significant difference in severity of apathy was found between STN DBS and medication only (g = 0.36, 95% CI = 0.03–0.65; P = 0.004). Statistical heterogeneity was moderately high, but the effects stood strong after multiple analyses and were independent of tapering off dopaminergic medication. The findings of this meta-analysis indicate that apathy is increased after STN DBS compared to the pre-operative state and to medication only (systematic review registration number: PROSPERO CRD42019133932). © 2020 Universiteit van Amsterdam. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society     

Histological Alterations Induced by Electrode Implantation and Electrical Stimulation in the Human Brain: A Review

Objectives. Electrical brain stimulation is used as a treatment for patients with intractable chronic pain and movement disorders. However, the implantation of electrodes and electrical stimulation may induce histological changes around the electrode tip. We aimed to review the histological changes in humans that were electrically stimulated in the brain. Methods. We traced 26 autopsy studies of which 19 patients received cerebellar stimulation and 37 patients deep brain stimulation. Results. Electrode implantation and electrical stimulation induced in part of the cases formation of a fibrous sheath around the electrode, loss of fairly large neurons, and limited gliosis. Macroscopic lesions were present in only some cases, mostly due to pulling at the extension cable in the postoperative evaluation period preceding definite implantation of the electrode wire and stimulator. Conclusions. Electrical brain stimulation induces histological changes in some patients. According to electrical brain stimulation studies in animals, these changes can be related to the charge and charge density per phase (and their interaction).     

Increased Subthalamic Nucleus Deep Brain Stimulation Amplitude Impairs Inhibitory Control of Eye Movements in Parkinson's Disease

Background and ObjectivesBilateral subthalamic nucleus deep brain stimulation (STN DBS) in Parkinson's disease (PD) can have detrimental effects on eye movement inhibitory control. To investigate this detrimental effect of bilateral STN DBS, we examined the effects of manipulating STN DBS amplitude on inhibitory control during the antisaccade task. The prosaccade error rate during the antisaccade task, that is, directional errors, was indicative of impaired inhibitory control. We hypothesized that as stimulation amplitude increased, the prosaccade error rate would increase.Materials and MethodsTen participants with bilateral STN DBS completed the antisaccade task on six different stimulation amplitudes (including zero amplitude) after a 12-hour overnight withdrawal from antiparkinsonian medication.ResultsWe found that the prosaccade error rate increased as stimulation amplitude increased (p < 0.01). Additionally, prosaccade error rate increased as the modeled volume of tissue activated (VTA) and STN overlap decreased, but this relationship depended on stimulation amplitude (p = 0.04).ConclusionsOur findings suggest that higher stimulation amplitude settings can be modulatory for inhibitory control. Some individual variability in the effect of stimulation amplitude can be explained by active contact location and VTA-STN overlap. Higher stimulation amplitudes are more deleterious if the active contacts fall outside of the STN resulting in a smaller VTA-STN overlap. This is clinically significant as it can inform clinical optimization of STN DBS parameters. Further studies are needed to determine stimulation amplitude effects on other aspects of cognition and whether inhibitory control deficits on the antisaccade task result in a meaningful impact on the quality of life.     

Neurochemical Control of Rapid Stress‐Induced Changes in Brain Aromatase Activity

In the male brain, the medial preoptic nucleus (POM) is known to be a critical relay for the activation of sexual behaviour, with the aromatisation of testosterone into 17β‐oestradiol (E₂) playing a key role. Acute stress has been shown to differentially modulate the aromatase enzyme in this and other brain nuclei in a sex‐specific manner. In POM specifically, stress induces increases in aromatase activity (AA) that are both rapid and reversible. How the physiological processes initiated during an acute stress response mediate sex‐ and nuclei‐ specific changes in AA and which stress response hormones are involved remains to be determined. By examining the relative effects of corticosterone (CORT), arginine vasotocin (AVT, the avian homologue to arginine vasopressin) and corticotrophin‐releasing factor (CRF), the present study aimed to define the hormone profile regulating stress‐induced increases in AA in the POM. We found that CORT, AVT and CRF all appear to play some role in these changes in the male brain. In addition, these effects occur in a targeted manner, such that modulation of the enzyme by these hormones only occurs in the POM rather than in all aromatase‐expressing nuclei. Similarly, in the female brain, the experimental effects were restricted to the POM but only CRF was capable of inducing the stress‐like increases in AA. These data further demonstrate the high degree of specificity (nuclei‐, sex‐ and hormone‐specific effects) in this system, highlighting the complexity of the stress–aromatase link and suggesting modes through which the nongenomic modulation of this enzyme can result in targeted, rapid changes in local oestrogen concentrations.