Did We Get Sensorimotor Adaptation Wrong? Implicit Adaptation as Direct Policy Updating Rather than Forward-Model-Based Learning

The human motor system can rapidly adapt its motor output in response to errors. The prevailing theory of this process posits that the motor system adapts an internal forward model that predicts the consequences of outgoing motor commands and uses this forward model to plan future movements. However, despite clear evidence that adaptive forward models exist and are used to help track the state of the body, there is no definitive evidence that such models are used in movement planning. An alternative to the forward-model-based theory of adaptation is that movements are generated based on a learned policy that is adjusted over time by movement errors directly (“direct policy learning”). This learning mechanism could act in parallel with, but independent of, any updates to a predictive forward model. Forward-model-based learning and direct policy learning generate very similar predictions about behavior in conventional adaptation paradigms. However, across three experiments with human participants (N = 47, 26 female), we show that these mechanisms can be dissociated based on the properties of implicit adaptation under mirror-reversed visual feedback. Although mirror reversal is an extreme perturbation, it still elicits implicit adaptation; however, this adaptation acts to amplify rather than to reduce errors. We show that the pattern of this adaptation over time and across targets is consistent with direct policy learning but not forward-model-based learning. Our findings suggest that the forward-model-based theory of adaptation needs to be re-examined and that direct policy learning provides a more plausible explanation of implicit adaptation.SIGNIFICANCE STATEMENT The ability of our brain to adapt movements in response to error is one of the most widely studied phenomena in motor learning. Yet, we still do not know the process by which errors eventually result in adaptation. It is known that the brain maintains and updates an internal forward model, which predicts the consequences of motor commands, and the prevailing theory of motor adaptation posits that this updated forward model is responsible for trial-by-trial adaptive changes. Here, we question this view and show instead that adaptation is better explained by a simpler process whereby motor output is directly adjusted by task errors. Our findings cast doubt on long-held beliefs about adaptation.     

联合应用mTI-ASL和IVIM技术在鉴别高级别胶质瘤术后复发与假性进展中的应用价值

目的: 探讨应用多反转时间动脉自旋标记(multiple inversion time-pulsed arterial spin labeling,mTI-ASL)和体素内不相干运动(intravoxel incoherent motion,IVIM)技术在脑胶质瘤术后复发与假性进展中的鉴别价值。方法: 选择2018年01月至2020年01月就诊于我院高级别胶质瘤术后放化疗后首次复查常规MR增强扫描出现异常强化的患者,行mTI-ASL及IVIM序列扫描,将获取图像数据资料进行相关后处理分析,分别手动勾画感兴趣区,测量术后异常强化区各项定量参数,即真性扩散系数(true diffusion coefficient,D)、假性扩散系数(pseudo-diffusion coefficient,D*)及灌注分数(perfusion fraction,f)、脑血流量(cerebral blood flow,CBF)和动脉通过时间(arterial transit time,ATT)。分别采用独立样本t检验比较两组感兴趣区相关参数值,从而评估mTI-ASL和IVIM技术在两者鉴别诊断中的价值。结果: (1)脑胶质瘤术后复发组CBF值(6.413±0.438)、ATT值(0.198±0.033),比假性进展组CBF值(4.654±0.372)、ATT值(0.165±0.208)高,两者比较具有统计学意义(P＜0.01)。(2)脑胶质瘤术后复发组D值(1.118±0.178),比假性进展组D值(1.380±0.236)低,两者比较具有统计学意义(P＜0.01)。(3)脑胶质瘤术后复发组D*值(17.126±4.274)、f值(0.269±0.095),比假性进展组D*值(12.755±3.974)、f值(0.169±0.052)高,两者比较具有统计学意义(P＜0.01)。结论:应用 mTI-ASL和IVIM技术有助于脑胶质瘤术后复发与假性进展的鉴别诊断。     

Computational fluid dynamics evaluation of flow reversal treatment of giant basilar tip aneurysm

Therapeutic parent artery flow reversal is a treatment option for giant, partially thrombosed basilar tip aneurysms. The effectiveness of this treatment has been variable and not yet studied by applying computational fluid dynamics. Computed tomography images and blood flow velocities acquired with transcranial Doppler ultrasonography were obtained prior to and after bilateral endovascular vertebral artery occlusion for a giant basilar tip aneurysm. Patient-specific geometries and velocity waveforms were used in computational fluid dynamics simulations in order to determine the velocity and wall shear stress changes induced by treatment. Therapeutic parent artery flow reversal lead to a dramatic increase in aneurysm inflow and wall shear stress (30 to 170 Pa) resulting in an increase in intra-aneurysmal circulation. The enlargement of the circulated area within the aneurysm led to a re-normalization of the wall shear stress and the aneurysm remained stable for more than 8 years thereafter. Therapeutic parent artery flow reversal can lead to unintended, potentially harmful changes in aneurysm inflow which can be quantified and possibly predicted by applying computational fluid dynamics.     

Reversal of idiopathic hypogonadotropic hypogonadism: a cohort study in Chinese patients

Although idiopathic hypogonadotropic hypogonadism (IHH) has traditionally been viewed as a life-long disease caused by a deficiency of gonadotropin-releasing hormone neurons, a portion of patients may gradually regain normal reproductive axis function during hormonal replacement therapy. The predictive factors for potential IHH reversal are largely unknown. The aim of our study was to investigate the incidence and clinical features of IHH male patients who had reversed reproductive axis function. In this retrospective cohort study, male IHH patients were classified into a reversal group (n = 18) and a nonreversal group (n = 336). Concentration of gonadotropins and testosterone, as well as testicle sizes and sperm counts, were determined. Of 354 IHH patients, 18 (5.1%) acquired normal reproductive function during treatment. The median age for reversal was 24 years old (range 21–34 years). Compared with the nonreversal group, the reversible group had higher basal luteinizing hormone (LH) (1.0 ± 0.7 IU l^-1 vs 0.4 ± 0.4 IU l⁻¹, P < 0.05) and stimulated LH (28.3 ± 22.6 IU l⁻¹ vs 1.9 ± 1.1 IU l⁻¹, P < 0.01) levels, as well as larger testicle size (5.1 ± 2.6 ml vs 1.5 ± 0.3 ml, P < 0.01), at the initial visit. In summary, larger testicle size and higher stimulated LH concentrations are favorite parameters for reversal. Our finding suggests that reversible patients may retain partially active reproductive axis function at initial diagnosis.     

复发难治性急性白血病多药耐药性及耐药逆转的体内外研究

目的 :探讨复发难治性急性白血病多药耐药性及耐药性的逆转。方法 :采用RT PCR法检测白血病细胞的多药耐药性 ,采用MTT法进行体外药敏及耐药逆转试验。结果 :35例患者中MDR1mRNA阳性表达例数为 2 6例(74.3% ) ,体外耐药逆转环胞素组逆转率 6 4.7%、异搏定组 41.2 %、两药合用组 76 .5 % ;临床耐药逆转环胞素组逆转率 14.3%、异搏定组 45 .8%、两药合用 37.5 % ;结论 :复发难治性急性白血病MDR1mRAN高表达 ,环胞素和异搏定单用及两药联合应用体外逆转效果明显优于临床疗效 ,耐药逆转药物的剂量及给药方式可能是影响逆转疗效的重要因素     

Reversal theory states and cigarette availability predict lapses during smoking cessation among adolescents

Although 67% of adolescent smokers say they want to quit, only 7% are able to do so. The purpose of this study was to use metamotivational states as described in reversal theory to predict whether adolescents who are trying to quit smoking will lapse (smoke a cigarette) or will resist smoking in highly tempting situations. Reversal theory holds that individuals switch between telic (serious-minded) and paratelic (playful) metamotivational states. Questionnaires and semistructured interviews were administered to 62 adolescents ages 14-19 who had participated in a smoking cessation program. Interviews were coded according to the Metamotivational State Interview and Coding Schedule, and the resulting data were analyzed using logistic regression analysis. Adolescents in the paratelic metamotivational state (OR = 15.34; 95% CI: 5.3, 43.6) or with cigarettes readily available (OR = 4.6; 95% CI: 1.6, 13.2) were more likely to lapse than were adolescents in the telic state or who required effort to obtain cigarettes. The variables telic/paratelic state and cigarette availability accurately predicted the outcome of highly tempting situations 80% of the time. Using reversal theory constructs to develop state-specific strategies shows promise as an additional tool for those in this age group coping with the temptation to smoke.     

Shared Neuropathological Characteristics of Obesity,Type 2 Diabetes and Alzheimer’s Disease: Impacts on Cognitive Decline

In the past few decades, the prevalence of obesity and type 2 diabetes mellitus (T2DM), as well as older individuals at risk for Alzheimer’s disease (AD), has increased. While the consumption of diets high in fat (total and saturated) have been linked to increased risk of AD, diets rich in antioxidants, polyunsaturated fats, and omega-3 fatty acids are associated with decreased risk. Additionally, AD patients are at increased risk for developing T2DM. Recent research suggests that there are stronger similarities between AD and T2DM than have previously been considered. Here we review the neurocognitive and inflammatory effects of high-fat diet consumption, its relationship to AD, and the treatment potential of dietary interventions that may decrease risk of cognitive decline and other associated neuropathological changes, such as insulin resistance, oxidative stress, and chronic inflammatory processes.