Endovascular deep brain stimulation: Investigating the relationship between vascular structures and deep brain stimulation targets

BackgroundEndovascular delivery of current using ‘stentrodes’ – electrode bearing stents – constitutes a potential alternative to conventional deep brain stimulation (DBS). The precise neuroanatomical relationships between DBS targets and the vascular system, however, are poorly characterized to date.ObjectiveTo establish the relationships between cerebrovascular system and DBS targets and investigate the feasibility of endovascular stimulation as an alternative to DBS.MethodsNeuroanatomical targets as employed during deep brain stimulation (anterior limb of the internal capsule, dentatorubrothalamic tract, fornix, globus pallidus pars interna, medial forebrain bundle, nucleus accumbens, pedunculopontine nucleus, subcallosal cingulate cortex, subthalamic nucleus, and ventral intermediate nucleus) were superimposed onto probabilistic vascular atlases obtained from 42 healthy individuals. Euclidian distances between targets and associated vessels were measured. To determine the electrical currents necessary to encapsulate the predefined neurosurgical targets and identify potentially side-effect inducing substrates, a preliminary volume of tissue activated (VTA) analysis was performed.ResultsSix out of ten DBS targets were deemed suitable for endovascular stimulation: medial forebrain bundle (vascular site: P1 segment of posterior cerebral artery), nucleus accumbens (vascular site: A1 segment of anterior cerebral artery), dentatorubrothalamic tract (vascular site: s2 segment of superior cerebellar artery), fornix (vascular site: internal cerebral vein), pedunculopontine nucleus (vascular site: lateral mesencephalic vein), and subcallosal cingulate cortex (vascular site: A2 segment of anterior cerebral artery). While VTAs effectively encapsulated mfb and NA at current thresholds of 3.5 V and 4.5 V respectively, incremental amplitude increases were required to effectively cover fornix, PPN and SCC target (mean voltage: 8.2 ± 4.8 V, range: 3.0–17.0 V). The side-effect profile associated with endovascular stimulation seems to be comparable to conventional lead implantation. Tailoring of targets towards vascular sites, however, may allow to reduce adverse effects, while maintaining the efficacy of neural entrainment within the target tissue.ConclusionsWhile several challenges remain at present, endovascular stimulation of select DBS targets seems feasible offering novel and exciting opportunities in the neuromodulation armamentarium.     

Prospective Analysis Using a Novel CNN Algorithm to Distinguish Atypical Ductal Hyperplasia From Ductal Carcinoma in Situ in Breast

IntroductionWe previously developed a convolutional neural networks (CNN)-based algorithm to distinguish atypical ductal hyperplasia (ADH) from ductal carcinoma in situ (DCIS) using a mammographic dataset. The purpose of this study is to further validate our CNN algorithm by prospectively analyzing an unseen new dataset to evaluate the diagnostic performance of our algorithm.Materials and MethodsIn this institutional review board-approved study, a new dataset composed of 280 unique mammographic images from 140 patients was used to test our CNN algorithm. All patients underwent stereotactic-guided biopsy of calcifications and underwent surgical excision with available final pathology. The ADH group consisted of 122 images from 61 patients with the highest pathology diagnosis of ADH. The DCIS group consisted of 158 images from 79 patients with the highest pathology diagnosis of DCIS. Two standard mammographic magnification views (craniocaudal and mediolateral/lateromedial) of the calcifications were used for analysis. Calcifications were segmented using an open source software platform 3D slicer and resized to fit a 128 × 128 pixel bounding box. Our previously developed CNN algorithm was used. Briefly, a 15 hidden layer topology was used. The network architecture contained 5 residual layers and dropout of 0.25 after each convolution. Diagnostic performance metrics were analyzed including sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve. The “positive class” was defined as the pure ADH group in this study and thus specificity represents minimizing the amount of falsely labeled pure ADH cases.ResultsArea under the receiver operating characteristic curve was 0.90 (95% confidence interval, ± 0.04). Diagnostic accuracy, sensitivity, and specificity was 80.7%, 63.9%, and 93.7%, respectively.ConclusionProspectively tested on new unseen data, our CNN algorithm distinguished pure ADH from DCIS using mammographic images with high specificity.     

Easy Words: Reference Resolution in a Malevolent Referent World

This article describes early stages in the acquisition of a first vocabulary by infants and young children. It distinguishes two major stages, the first of which operates by a stand‐alone word‐to‐world pairing procedure and the second of which, using the evidence so acquired, builds a domain‐specific syntax‐sensitive structure‐to‐world pairing procedure. As we show, the first stage of learning is slow, restricted in character, and to some extent errorful, whereas the second procedure is determinative, rapid, and essentially errorless. Our central claim here is that the early, referentially based learning procedure succeeds at all because it is reined in by attention‐focusing properties of word‐to‐world timing and related indicants of referential intent.     

Reduced regional homogeneity and neurocognitive impairment in patients with moderate-to-severe obstructive sleep apnea

BackgroundNeurocognitive dysfunction and abnormal regional homogeneity (ReHo) have been reported in patients with obstructive sleep apnea (OSA). However, little is known about whether brain functional alteration could be used to differentiate from healthy controls (HCs) and its correlation with neurocognitive impairment.MethodsThirty-three treatment-naive patients with moderate-to-severe OSA and 22 HCs with matched age, sex and education underwent the evaluation of Epworth sleepiness scale, neurocognitive function, full night polysomnography and resting-state functional magnetic resonance imaging scan. ReHo, support vector machine, and correlation with neurocognitive function were administrated to analyze the data.ResultsCompared with HCs, patients with OSA showed decreased ReHo in the bilateral superior frontal gyrus (FG), bilateral superior medial prefrontal cortex (PFC)/right supplementary motor area (SMA), left middle FG, and right precentral/postcentral gyrus. Negative correlations were observed between the ReHo values in the left superior FG/middle FG and apnea hypopnea index, oxygen desaturation index in the OSA group. The scores of Stroop word test, Stroop color-word test, symbol coding test were all negatively correlated with the ReHo values in the right precentral gyrus/postcentral gyrus in patients. Scores of the animal naming fluency test were positively correlated with the ReHo values in the left superior FG/middle FG in patients. Moreover, support vector machine analysis showed the ReHo values in the left superior FG/middle FG or bilateral superior medial PFC/right SMA both could discriminate patients from HCs with good accuracies, sensitivities, and specificities (85.45%, 87.88%, 81.82% and 81.82%, 84.85%, 77.27%, respectively).ConclusionDysfunction in the frontal lobe is a potentially pivotal neuro-pathophysiological mechanism of neurocognitive impairment in patients with moderate-to-severe OSA. And significantly lower ReHo values in the left superior FG/middle FG and/or superior medial PFC/SMA are promising imaging biomarkers to discriminate moderate-to-severe patients with OSA from HCs.     

口腔病理学研究性学习教学改革的尝试

为了培养有自学能力、信息获取能力、沟通能力和临床思维能力的高素质医学人才,建立适应人才培养需要的口腔病理学教学方法,本文采用行动研究方法,对基于问题解决为中心、研究性学习的教学方法进行了实验性研究,旨在探讨如何充分利用网络资源进行口腔医学教学改革的思路,希望对今后教学改革具有启示作用。     

Differential role for the striatum and cerebellum in response to novel movements using a motor learning paradigm.

The aim of this pilot study was to examine the role of the striatum and cerebellum in the adaptation to a novel movement within a sequence of practiced movements using a motor learning paradigm. The performance of patients in the early or advanced stages of Parkinson's disease (PD) and of patients with damage to the cerebellum (CE) was compared, respectively to a group of aged and young matched controls on an adapted version of the Mirror-Tracing Test. In this task, subjects were required to trace a series of complex figures in two conditions: (1) a Practiced condition, in which the figures were composed of the juxtaposition of three simple designs that were extensively practiced before; and (2) a Mixed condition in which triads were created by replacing the last simple figure of the triads in the Practiced condition by a new simple figure that had never been traced individually before. Results showed that all clinical groups were slower than controls at tracing the Practiced triads. Most interestingly, however, only patients in the advanced stages of PD showed increased completion time to trace the triads in the Mixed condition. This suggests that a bilateral striatal dysfunction affects the ability to adapt to a novel motion within a sequence of practiced movements. Although exploratory, these results support a functional dissociation between the striatum and cerebellum in acquiring visuomotor skilled behaviors.     

Effects of acute administration of d-amphetamine and haloperidol on procedural learning in man

The effects of an indirect dopamine-agonist, d-amphetamine, and a non-selective dopamine receptor antagonist, haloperidol, were investigated in normal male volunteers using a between-subjects double-blind design in a procedural learning task, thought mainly to involve unconscious/automatic learning. The results showed: (1) d-amphetamine facilitated response speed, whereas haloperidol inhibited it, in comparison to placebo; (2) the linear increase in procedural learning corresponded with pharmacological manipulation of degree of dopaminergic activity, i.e. subjects given haloperidol showed the least, and subjects given d-amphetamine the greatest, procedural learning. The implications of these findings are discussed in relation to investigation of abnormalities of procedural learning processes in schizophrenia. Received: 28 June 1996/Final version: 2 October 1996     

Long-term neurotoxicity of chlorpyrifos: spatial learning impairment on repeated acquisition in a water maze.

Organophosphate compounds are cholinesterase inhibitors widely used in agriculture, industry, household products, and even as chemical weapons. Their major mechanism of acute toxic action is the inhibition of acetylcholinesterase, which is responsible for the degradation of the neurotransmitter acetylcholine. An organophosphorus ester-induced chronic neurotoxicity (OPICN) syndrome has been proposed. The OPICN syndrome could result from both long-term exposure to subclinical doses of OPs and after acute poisoning. Development of animal models for the cognitive decline are required and could later help to elucidate the mechanisms involved in this long-term effect on the central nervous system. Previously, we have found performance decrements in a four-trial repeated acquisition spatial task in a water maze. The present study includes two experiments to extend the long-term behavioral effects observed. Rats were injected either once or twice with chlorpyrifos (CPF) and then tested months after in a two-trial repeated acquisition task in a water maze. Our results confirm and extend the long-term behavioral effects of subcutaneous administration of CPF. The two treatments used produced performance decrements that suggest functional central nervous system alterations.     

石杉碱甲和乙促进小鼠的空间辨别学习和记忆

石杉碱甲和乙是从石杉科石杉属植物蛇足石杉[Huperzia scrrata(Thunb.)Trev.]中分得的二个新生物碱。“Y”迷宫实验表明,ip Hup-A 0.075～0.125 mg/kg或Hup-B 0.4～0.8mg/kg,均能明显促进小鼠的空间辨别学习,并能显著预防CO₂产生的短时识别障碍,促进记忆保持和记忆再现。ig Hup-A 0.1～0.3 mg/kg或Hup-B 0.8 mg/kg也有促进学习的作用。促进作用Hup-A>Phys>Hup-B。剂量与效应曲线呈倒U型。