Commentary: Broadening the research remit of participatory methods in autism science – a commentary on Happé and Frith (2020)

Autism science has transformed beyond recognition in the last two decades. International investment has grown extensively and the number of papers published on autism has increased 10-fold (Pellicano et al., 2014), far surpassing publications on related topics. The sheer amount of scientific research on autism has no doubt been instrumental in many of the discoveries and insights so eloquently described by Happé and Frith (2020). But, as autistic scientist Michelle Dawson reminds us, quality matters too and, for that reason, it is a delight to recognise the contribution that both Happé and Frith have made, dramatically changing our understanding of autism in a host of ways.     

Structured Sequence Learning: Animal Abilities,Cognitive Operations,and Language Evolution

Human language is a salient example of a neurocognitive system that is specialized to process complex dependencies between sensory events distributed in time, yet how this system evolved and specialized remains unclear. Artificial Grammar Learning (AGL) studies have generated a wealth of insights into how human adults and infants process different types of sequencing dependencies of varying complexity. The AGL paradigm has also been adopted to examine the sequence processing abilities of nonhuman animals. We critically evaluate this growing literature in species ranging from mammals (primates and rats) to birds (pigeons, songbirds, and parrots) considering also cross‐species comparisons. The findings are contrasted with seminal studies in human infants that motivated the work in nonhuman animals. This synopsis identifies advances in knowledge and where uncertainty remains regarding the various strategies that nonhuman animals can adopt for processing sequencing dependencies. The paucity of evidence in the few species studied to date and the need for follow‐up experiments indicate that we do not yet understand the limits of animal sequence processing capacities and thereby the evolutionary pattern. This vibrant, yet still budding, field of research carries substantial promise for advancing knowledge on animal abilities, cognitive substrates, and language evolution.     

Risk factors for neurocognitive decline in lung cancer patients treated with prophylactic cranial irradiation: A systematic review

BackgroundProphylactic cranial irradiation (PCI) reduces brain metastasis incidence in lung cancer, however with risk of neurocognitive decline. Nevertheless, risk factors for neurocognitive decline after PCI remain unclear.MethodsWe systematically reviewed the PubMed database according to the PRISMA guideline. Inclusion criteria were: randomized clinical trials (RCTs) and observational/single arm trials evaluating PCI, including ≥20 patients, reporting neurocognitive test results for lung cancer. Primary aim: evaluate risk factors associated with neurocognitive decline after PCI.ResultsTwenty records were eligible (8 different RCTs, 8 observational studies), including 3553 patients in total (858 NSCLC, 2695 SCLC) of which 73.6% received PCI. Incidence of mild/moderate cognitive decline after PCI varied from 8 to 89% (grading not always provided); for those without PCI, this was 3.4–42%. Interestingly, 23–95% had baseline cognitive impairment. Risk factors were often not reported. In one trial, both age (>60 years) and higher PCI dose (36 Gy) including twice-daily PCI were associated with a higher risk of cognitive decline. In one trial, white matter abnormalities were more frequent in the concurrent or sandwiched PCI arm, but without significant neuropsychological differences. One trial identified hippocampal sparing PCI to limit the neurocognitive toxicities of PCI and another reported an association between hippocampal dose volume effects and memory decline. As neurocognition was a secondary endpoint in most RCTs, and was assessed by various instruments with often poor/moderate compliance, high-quality data is lacking.ConclusionsAge, PCI dose, regimen and timing might be associated with cognitive impairment after PCI in lung cancer patients, but high-quality data is lacking. Future PCI trials should collect and evaluate possible risk factors systematically.     

Reliability of gait and dual-task measures in multiple sclerosis

BackgroundSingle-task (ST) and dual-task (DT) assessments are commonly used to evaluate motor and cognitive impairment in people with multiple sclerosis (MS). Although variability can influence repeated DT testing measures, the reliability of several DT variables over time has not been adequately explored. For instance, a third testing session has never been included to observe whether DT has a learning effect. DT cognition rate reliability has not yet been examined and dual-task cost (DTC), a widely used calculation for DT interpretation, has not been proven reliable.Research questionTo evaluate the reliability of ST and DT measures of gait and cognition over three test sessions.MethodsThis was a cross-sectional study involving 18 people with MS and 12 controls. Participants attended three test sessions, each one week apart. ST and DT (serial seven subtraction) gait variables, DTC, coefficient of variability (CV), and cognition rate were extracted and calculated using an instrumented walkway. Reliability was assessed using intraclass correlation coefficients (ICC) or Kendall’s coefficient of concordance (KCC; nonparametric test) and minimum detectable change (MDC); between-session learning effect was assessed using repeated measures ANOVA.ResultsICC/KCC values for ST and DT gait variables ranged from moderate to excellent (0.50-0.99). However, reliability for DT stride width and cognition rate was lower in controls. In general, DTC and CV variables had poor ICCs and high MDC values (49.19–1478.67 %), although some DTC variables had moderate or higher reliability in controls. Cognition rate was reliable in both MS (ICC 0.91) and controls (ICC 0.84). A learning effect between sessions was observed for DT velocity in both groups and for DTC cadence in people with MS.SignificanceST and DT gait measures as well as DT cognition rate are reliable outcomes for repeated testing, while DTC and CV variables may not be suitable for long-term monitoring.     

肝移植术后认知与脑改变的多模态神经成像

肝性脑病是终末期肝硬化的重要并发症,导致病人出现一系列神经及认知功能改变。肝移植术后病人在肝功能恢复的同时其认知功能也可明显改善。MRI可以从脑代谢、结构及功能方面更进一步揭示肝硬化病人移植术后认知及脑改变情况。综述肝移植术后认知改变的研究现状以及最新的多模态MRI技术在术后脑改变中的应用,及其在揭示术后认知恢复及残存损害的神经机制中的价值。     

Chemogenetic Silencing of the Locus Coeruleus–Basolateral Amygdala Pathway Abolishes Pain-Induced Anxiety and Enhanced Aversive Learning in Rats

BackgroundPain affects both sensory and emotional aversive responses, often provoking anxiety-related diseases when chronic. However, the neural mechanisms underlying the interactions between anxiety and chronic pain remain unclear.MethodsWe characterized the sensory, emotional, and cognitive consequences of neuropathic pain (chronic constriction injury) in a rat model. Moreover, we determined the role of the locus coeruleus (LC) neurons that project to the basolateral amygdala (BLA) using a DREADD (designer receptor exclusively activated by designer drugs).ResultsChronic constriction injury led to sensorial hypersensitivity in both the short term and long term. Otherwise, long-term pain led to an anxiety-like profile (in the elevated zero maze and open field tests), as well as increased responses to learn aversive situations (in the passive avoidance and fear conditioning tests) and an impairment of nonemotional cognitive tasks (in the novel object recognition and object pattern of separation tests). Chemogenetic blockade of the LC-BLA pathway and intra-BLA or systemic antagonism of beta-adrenergic receptors abolished both long-term pain-induced anxiety and enhanced fear learning. By contrast, chemogenetic activation of this pathway induced anxiety-like behaviors and enhanced the aversive learning and memory index in sham animals, although it had little effect on short- and long-term chronic constriction injury animals. Interestingly, modulation of LC-BLA activity did not modify sensorial perception or episodic memory.ConclusionsOur results indicate that dimensions associated with pain are processed by independent pathways and that there is an overactivation of the LC-BLA pathway when anxiety and chronic pain are comorbid, which involves the activity of beta-adrenergic receptors.     

阿尔茨海默病患者的执行功能障碍

目的了解阿尔茨海默病(A lzhe im er d isease,AD)患者执行功能损害状况及对于生活能力的影响,探讨执行功能障碍与记忆等AD常见认知功能损害的相关性。方法运用神经心理学测验的方法对40例AD患者及30例轻度认知功能损害(m ild cogn itive impairm ent,MC I)患者进行执行功能、记忆及其他认知功能检查,同时进行生活能力评定。另外选择40名健康老人作对照。结果AD组的执行功能测验成绩均显著低于健康对照组(P<0.01),其中额叶功能评定量表(FAB)(5.29±2.47)分,执行性画钟作业(CLOX1)(4.63±3.56)分,Stroop测验错误次数(Stroop1)(14.17±8.99)分,词语流畅性测验(RVR)(17.56±10.51)分。除Stroop测验反应时间(Stroop2)外,MC I组的其他执行功能测验成绩显著低于健康对照组(P<0.05),其中FAB为(7.67±2.44)分,CLOX1为(7.86±3.78)分,Stroop1为(7.21±8.07)分,RVR为(30.86±8.38)分。用多元逐步回归方法分析不同认知功能对生活能力的影响,结果为反映执行功能的FAB测验成绩处于第一位,独立与操作性日常生活能力(IADL)相关(β=-0.778,t=-7.079,P<0.01)。各项执行功能测验与年龄相关性不明显(r=0.026~0.250,P>0.05),与简易精神状态量表(MMSE)、记忆测验成绩相关性好(r=0.438~0.786,P<0.01)。结论AD患者具有明显的执行功能障碍;在尚未到达痴呆水平的MC I阶段也可发现执行功能损害。执行功能和整体认知功能及记忆等认知域功能具有良好的相关性。AD患者的执行功能障碍是导致生活能力下降的重要因素。     

阿尔茨海默病患者脑白质损害与认知功能的关系

目的用磁共振扩散张量成像(DTI)研究阿尔茨海默病(AD)患者脑白质损害的特点及其与认知功能改变的相关性。方法对16例AD患者和12名年龄及性别相当的健康老年人行DTI、T1液体衰减反转恢复序列(FLAIR)及T2-FLAIR检查,测量胼胝体膝部和压部、内囊前肢和后肢、额颞顶枕叶白质的部分各向异性分数值(FA)和平均弥散度(MD),分析FA、MD值与简易精神状态量表(MMSE)评分之间的相关关系。结果AD患者胼胝体压部、额叶、顶叶、颞叶FA值分别为0.602±0.043、0.270±0.034、0.294±0.043、0.302±0.032,与健康老人组相比显著下降(P<0.05),且与MMSE评分呈正相关关系,而内囊前后肢、枕叶、胼胝体膝部的FA值则无明显变化(P>0.05);胼胝体压部、顶叶白质的MD值分别为(0.918±0.029)、(0.826±0.015)×10-9m2/s,与健康老人组相比显著升高(P<0.01),且与MMSE评分呈负相关,而内囊前后肢、额叶、颞叶、枕叶和胼胝体膝部的MD值则无明显变化(P>0.05)。结论AD患者表现为脑白质的选择性损害,且损害程度与认知功能密切相关;这种选择性损害反映了AD病理机制中皮质-皮质及皮质-皮质下联系的丢失;DTI技术可以用来监测疾病的进展情况及评价AD治疗药物的临床疗效。