Putting perception into action: Inverse optimal control for continuous psychophysics

Psychophysical methods are a cornerstone of psychology, cognitive science, and neuroscience where they have been used to quantify behavior and its neural correlates for a vast range of mental phenomena. Their power derives from the combination of controlled experiments and rigorous analysis through signal detection theory. Unfortunately, they require many tedious trials and preferably highly trained participants. A recently developed approach, continuous psychophysics, promises to transform the field by abandoning the rigid trial structure involving binary responses and replacing it with continuous behavioral adjustments to dynamic stimuli. However, what has precluded wide adoption of this approach is that current analysis methods recover perceptual thresholds, which are one order of magnitude larger compared to equivalent traditional psychophysical experiments. Here we introduce a computational analysis framework for continuous psychophysics based on Bayesian inverse optimal control. We show via simulations and on previously published data that this not only recovers the perceptual thresholds but additionally estimates subjects' action variability, internal behavioral costs, and subjective beliefs about the experimental stimulus dynamics. Taken together, we provide further evidence for the importance of including acting uncertainties, subjective beliefs, and, crucially, the intrinsic costs of behavior, even in experiments seemingly only investigating perception.

Neural Response to Monetary and Social Feedback Demonstrate Differential Associations with Depression and Social Anxiety

An aberrant neural response to rewards has been linked to both depression and social anxiety. Most studies have focused on the neural response to monetary rewards, and few have tested different modalities of reward (e.g., social) that are more salient to particular forms of psychopathology. In addition, most studies contain critical confounds, including contrasting positive and negative feedback and failing to disentangle being correct from obtaining positive feedback. In the present study, 204 participants underwent electroencephalography during monetary and social feedback tasks that were matched in trial structure, timing, and feedback stimuli. The reward positivity (RewP) was measured in response to correctly identifying stimuli that resulted in monetary win, monetary loss, social like, or social dislike feedback. All monetary and social tasks elicited a RewP, which were positively correlated. Across all tasks, the RewP was negatively associated with depression and positively associated with social anxiety. The RewP to social dislike feedback, independent of monetary and social like feedback, was also associated with social anxiety. The present study suggests that a domain-general neural response to correct feedback demonstrates a differential association with depression and social anxiety, but a domain-specific neural response to social dislike feedback is uniquely associated with social anxiety.

A platform trial in practice: adding a new experimental research arm to the ongoing confirmatory FLAIR trial in chronic lymphocytic leukaemia

Background The FLAIR trial in chronic lymphocytic leukaemia has a randomised, controlled, open-label, confirmatory, platform design. FLAIR was successfully amended to include an emerging promising experimental therapy to expedite its assessment, greatly reducing the time to reach the primary outcome compared to running a separate trial and without compromising the validity of the research or the ability to recruit to the trial and report the outcomes. The methodological and practical issues are presented, describing how they were addressed to ensure the amendment was a success. Methods FLAIR was designed as a two-arm trial requiring 754 patients. In stage 2, two new arms were added: a new experimental arm and a second control arm to protect the trial in case of a change in practice. In stage 3, the original experimental arm was closed as its planned recruitment target was reached. In total, 1516 participants will be randomised to the trial. Results The changes to the protocol and randomisation to add and stop arms were made seamlessly without pausing recruitment. The statistical considerations to ensure the results for the original and new hypotheses are unbiased were approved following peer review by oversight committees, Cancer Research UK, ethical and regulatory committees and pharmaceutical partners. These included the use of concurrent comparators in case of any stage effect, appropriate control of the type I error rate and consideration of analysis methods across trial stages. The operational aspects of successfully implementing the amendments are described, including gaining approvals and additional funding, data management requirements and implementation at centres. Conclusions FLAIR is an exemplar of how an emerging experimental therapy can be assessed within an existing trial structure without compromising the conduct, reporting or validity of the trial. This strategy offered considerable resource savings and allowed the new experimental therapy to be assessed within a confirmatory trial in the UK years earlier than would have otherwise been possible. Despite the clear efficiencies, treatment arms are rarely added to ongoing trials in practice. This paper demonstrates how this strategy is acceptable, feasible and beneficial to patients and the wider research community. Trial registration ISRCTN Registry ISRCTN01844152. Registered on August 08, 2014

TO THE HISTORY OF KAZAKH TRIBES FORMATION OF BAIULY UNION

В данной статье рассматриваются этноисторические предпосылки формирования некоторых казахских племен, относящихся в триальной структуре кочевого населения Казахстана к объединению Байулы Младшего жуза. Реконструкция исторических этапов сложения казахских племен проводится путем определения возможных этнополитических контактов, существовавших, согласно письменным источникам и репрезентативным материалам устной историологии, между раннесредневековым населением, обитавшем на территории степного пространства западного Казахстана. Расселявшиеся здесь тюркоязычные племена представляли огузскую этническую общность (баяты, языры, салоры, авшары и др.), сыгравшую важную роль в становлении этнического ядра сложившихся много позднее племен казахского Младшего жуза. Исторические события начала II тыс. н. э. способствовали возникновению тесных контактов огузов с кыпчаками, что отложилось в генеалогических преданиях о происхождении байулинского поколения казахских племен. Исследование указанных сюжетов соответствует теоретическим подходам, основывающимся на известной концепции дахо-массагетского происхождения некоторых племен Младшего жуза, а также связующей роли огузского этнического компонента в образовании кыпчакской конфедерации племен на территории западного Казахстана. Изучение вопроса затрагивает анализ историографии, которая исходит из позиции преемственности этнополитических и этнокультурных процессов, шедших на территории Центральной Азии с эпохи древности до завершения формирования тюркских (в том числе и казахского) народов. Высказанные в ходе исследования учеными гипотезы, касающиеся разных аспектов этногенеза тюркских племен, были систематизированы и получили дальнейшее развитие и подтверждение путем компаративного анализа и проведения этноисторических параллелей этнонимии тюркских народов с данными традиционных письменных источников, топонимии и памятников устного народного творчества. Формирование этнической основы казахских племен Младшего жуза (западные и юго-западные районы) проходило в условиях тесной взаимосвязи этнических процессов, шедших на территории всего раннесредневекового Казахстана. This article discusses the ethnohistorical prerequisites for the formation of some Kazakh tribes belonging to the trial structure of Kazakhstan nomadic population, to the union Bayuli Younger Zhuzes of Kazakhstan. The reconstruction of the historical stages of the formation of the Kazakh tribes is carried out by identifying possible ethno-political contacts that existed at the time, according to written sources and representative materials of oral historiology, between the early medieval populations residing in the territory of western Kazakhstan steppe. The Turkic-speaking tribes settled here represented the Oguz ethnic community (bayats, yazirs, salors, avshars, etc.), which played an important role in the formation of the ethnic core of the consequently formed tribes of the Kazakh Younger zhuz. Historical events of the beginning of the 2nd millennium AD contributed to the emergence of close contacts of Oguz with Kypchaks, which was reflected in the genealogical legends on the origin of the Bayuli generation of Kazakh tribes. The study of these plots is consistent with theoretical approaches based on the well-known concept of the Dakho-Massaget origin of some tribes of the Younger Zhuz, as well as the connecting role of the Oghuz ethnic component in the formation of the Kypchak confederation of tribes in western Kazakhstan.

Fronto-parietal, cingulo-opercular and striatal contributions to learning and implementing control policies

Efficient task performance requires co-ordination of internal cognitive processes by implementing control policies adapted to the dynamic structure of task demands. The cognitive and neural basis of control policy implementation remains poorly characterized, in part because it is typically confounded with implementing new stimulus-response rules. To disambiguate these processes, we asked participants to perform multiple novel variants of a working memory control task. Each variant had a unique, novel sequential trial structure, but all shared common stimulusresponse rules, enabling us to test control policy implementation separate from rule learning. Behaviorally, we found evidence for two adaptive processes tied to control policy implementation. One process was reflected in slower responses on the first trial with a novel sequential trial structure, followed by rapid speeding on subsequent trials. A second process was reflected in the diminishing size of the first trial cost as participants accommodated different variants of the task over many blocks. Using fMRI, we observed that the striatum and a cingulo-opercular cortical network increased activity to the first trial, tracking the fast adjustment. This pattern of activity dissociated these regions from a fronto-parietal network including dorsolateral PFC, inferior frontal junction, inferior parietal sulcus, and rostrolateral PFC, which showed a slower decline in activity across trials, mirroring findings in rule implementation studies, but in the absence of rule implementation demands. Our results reveal two adaptive processes underlying the implementation of efficient, generalizable control policies, and suggest a broader account of the role of a cortico-striatal network in control policy implementation.Significance statementRapid adaptation to novel tasks is a hallmark of human behavior. Understanding how human brains achieve this is of critical importance in neuroscience. Here we broaden the scope of this problem, going beyond task rules to more broadly consider the cognitive control demands produced by novel task dynamics. We propose that humans rely on two adaptive processes to rapidly implement efficient, generalizable control policies as task dynamics change, even when task rules remain unchanged. One process unfolds rapidly and underlies efficient adaptation. A second process unfolds slowly with experience across task conditions and underlies generalization of control policies. Using fMRI, we identify cingulo-opercular cortex, fronto-parietal cortex and striatum as dissociable components of a cortico-striatal network that contribute to control implementation.

THE PHENOMENON OF THE GENESIS OF THE KAZAKH PEOPLE AND ETHNIC SYSTEM

The article examines the ethnic system of the Kazakh people. An attempt is made to answer the question: what influence did the ethnic system have on the ethnogenesis of the Kazakh people? The historical conditions for the formation and development of a people are reflected in the genesis of any ethnic group. The Kazakh people were born and developed under the influence of the standards of the tribal system. For more than one millennium, this system has retained its inviolability. Therefore, the ethnic system of the clan had a strong influence on the genesis of the Kazakh people. The tradition of the "trial" structure of the ethnic system of the patriarchal system contributed to the emergence of the cult of ancestors. Exogamy and polygamy of marital relations played an exceptional role in the ethnogenesis of the people, which ensured the "purity of the ranks".

Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT): A Bayesian Adaptive Platform Trial to Develop Precision Medicines for Patients With Glioblastoma

PURPOSE Adequately prioritizing the numerous therapies and biomarkers available in late-stage testing for patients with glioblastoma (GBM) requires an efficient clinical testing platform. We developed and implemented INSIGhT (Individualized Screening Trial of Innovative Glioblastoma Therapy) as a novel adaptive platform trial (APT) to develop precision medicine approaches in GBM. METHODS INSIGhT compares experimental arms with a common control of standard concurrent temozolomide and radiation therapy followed by adjuvant temozolomide. The primary end point is overall survival. Patients with newly diagnosed unmethylated GBM who are IDH R132H mutation negative and with genomic data available for biomarker grouping are eligible. At the initiation of INSIGhT, three experimental arms (neratinib, abemaciclib, and CC-115), each with a proposed genomic biomarker, are tested simultaneously. Initial randomization is equal across arms. As the trial progresses, randomization probabilities adapt on the basis of accumulating results using Bayesian estimation of the biomarker-specific probability of treatment impact on progression-free survival. Treatment arms may drop because of low probability of treatment impact on overall survival, and new arms may be added. Detailed information on the statistical model and randomization algorithm is provided to stimulate discussion on trial design choices more generally and provide an example for other investigators developing APTs. CONCLUSION INSIGhT (NCT02977780) is an ongoing novel biomarker-based, Bayesian APT for patients with newly diagnosed unmethylated GBM. Our goal is to dramatically shorten trial execution timelines while increasing scientific power of results and biomarker discovery using adaptive randomization. We anticipate that trial execution efficiency will also be improved by using the APT format, which allows for the collaborative addition of new experimental arms while retaining the overall trial structure.

Breathe Easy EDA: A MATLAB toolbox for psychophysiology data management, cleaning, and analysis

Electrodermal activity (EDA) recordings are widely used in experimental psychology to measure skin conductance responses (SCRs) that reflect sympathetic nervous system arousal. However, irregular respiration patterns and deep breaths can cause EDA fluctuations that are difficult to distinguish from genuine arousal-related SCRs, presenting a methodological challenge that increases the likelihood of false positives in SCR analyses. Thus, it is crucial to identify respiration-related artifacts in EDA data. Here we developed a novel and freely distributed MATLAB toolbox, Breathe Easy EDA (BEEDA). BEEDA is a flexible toolbox that facilitates EDA visual inspection, allowing users to identify and eliminate respiration artifacts. BEEDA further includes functionality for EDA data analyses (measuring tonic and phasic EDA components) and reliability analyses for artifact identification. The toolbox is suitable for any experiment recording both EDA and respiration data, and flexibly adjusts to experiment-specific parameters (e.g., trial structure and analysis parameters).

Breathe Easy EDA: A MATLAB toolbox for psychophysiology data management, cleaning, and analysis

Electrodermal activity (EDA) recordings are widely used in experimental psychology to measure skin conductance responses (SCRs) that reflect sympathetic nervous system arousal. However, irregular respiration patterns and deep breaths can cause EDA fluctuations that are difficult to distinguish from genuine arousal-related SCRs, presenting a methodological challenge that increases the likelihood of false positives in SCR analyses. Thus, it is crucial to identify respiration-related artifacts in EDA data. Here we developed a novel and freely distributed MATLAB toolbox, Breathe Easy EDA (BEEDA). BEEDA is a flexible toolbox that facilitates EDA visual inspection, allowing users to identify and eliminate respiration artifacts. BEEDA further includes functionality for EDA data analyses (measuring tonic and phasic EDA components) and reliability analyses for artifact identification. The toolbox is suitable for any experiment recording both EDA and respiration data, and flexibly adjusts to experiment-specific parameters (e.g., trial structure and analysis parameters).