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AbstractAlthough relatively costly and non-scalable, non-invasive neuromodulation interventions are treatment alternatives for neuropsychiatric disorders. The recent developments of highly-deployable transcranial electric stimulation (tES) systems, combined with mobile-Health technologies, could be incorporated in digital trials to overcome methodological barriers and increase equity of access. We convened 61 highly-productive specialists and contacted 8 tES companies to assess 71 issues related to tES digitalization readiness, and processes, barriers, advantages, and opportunities for implementing tES digital trials. Delphi-based recommendations (>60% agreement) were provided. Device appraisal showed moderate digitalization readiness, with high safety and the possibility of trial implementation, but low connectivity. Panelists recognized the potential of tES for scalability, generalizability, and leverage of digital trials processes; although they reached no consensus about aspects regarding methodological biases. We further propose and discuss a conceptual framework for exploiting shared aspects between mobile-Health tES technologies with digital trials methodology to drive future efforts for digitizing tES trials.Graphical Abstract. Consensus Roadmap(A) Recruitment process. The study procedure started with defining the components of the research problem by the core research team. After defining the problems, two different sets of participants (the steering committee (SC) including key leaders of the field identified by the core team and the expert panel (EP) as a more diverse group of experts identified based on the number of publications based on a systematic review) were identified and were invited to participate in a Delphi study. The study facilitators (first and last authors) led the communications with the SC to design the initial questionnaire through an iterative approach. (B) Evidence synthesis: To collect the available evidence, companies producing portable tES (ptES) devices were contacted, based on the companies suggested by the SC and EP to provide details about the available devices. For mapping methodological processes of digitizing tES trials, two distinct strategies were performed and embedded into the questionnaire, namely SIPOC (Suppliers, Inputs, Process, Outputs, and Customer) and SWOT (Strengths, Weaknesses, Opportunities, and Threats) assessment were performed and embedded into the questionnaire. (C) Consensus development: In the next phase, the questionnaire was validated and finalized via collecting and summarizing opinions. Afterward, the SC and EP responded to the final questionnaire, and results were analyzed providing a list of recommendations for running tES digital trials based on a pre-registered consensus threshold.

SummaryIndividual memories are often linked so that the recall of one triggers the recall of another. For example, contextual memories acquired close in time can be linked, and this is known to depend on temporary increase in excitability that drive the overlap between dorsal CA1 (dCA1) hippocampal ensembles encoding the linked memories. Here, we show that the Locus Coeruleus (LC) cells projecting to dCA1 have a key permissive role in contextual memory linking, without affecting contextual memory formation, and that this effect is mediated by dopamine and not by noradrenaline. Additionally, we found that LC to dCA1 projecting neurons modulate the excitability of dCA1 neurons, and the extent of overlap between dCA1 memory ensembles, as well as the stability of coactivity patterns within these ensembles. This discovery of a neuromodulatory system that specifically affects memory linking without affecting memory formation, reveals a fundamental separation between the brain mechanisms that modulate these two distinct processes.

The first issue of Nature Reviews Neuroscience was published 20 years ago, in 2000. To mark this anniversary, in this Viewpoint article we asked a selection of researchers from across the field who have authored pieces published in the journal in recent years for their thoughts on notable and interesting developments in neuroscience, and particularly in their areas of the field, over the past two decades. They also provide some thoughts on current lines of research and questions that excite them.

Structured information is easier to remember and recall than random one. In real life, information exhibits multi-level hierarchical organization, such as clauses, sentences, episodes and narratives in language. Here we show that multi-level grouping emerges even when participants perform memory recall experiments with random sets of words. To quantitatively probe brain mechanisms involved in memory structuring, we consider an experimental protocol where participants perform ‘final free recall’ (FFR) of several random lists of words each of which was first presented and recalled individually. We observe a hierarchy of grouping organizations of FFR, most notably many participants sequentially recalled relatively long chunks of words from each list before recalling words from another list. More-over, participants who exhibited strongest organization during FFR achieved highest levels of performance. Based on these results, we develop a hierarchical model of memory recall that is broadly compatible with our findings. Our study shows how highly controlled memory experiments with random and meaningless material, when combined with simple models, can be used to quantitatively probe the way meaningful information can efficiently be organized and processed in the brain, so to be easily retrieved.Significance StatementInformation that people communicate to each other is highly structured. For example, a story contains meaningful elements of various degrees of complexity (clauses, sentences, episodes etc). Recalling a story, we are chiefly concerned with these meaningful elements and not its exact wording. Here we show that people introduce structure even when recalling random lists of words, by grouping the words into ‘chunks’ of various sizes. Doing so improves their performance. The so formed chunks closely correspond in size to story elements described above. This suggests that our memory is trained to create a structure that resembles the one it typically deals with in real life, and that using random material like word lists can be used to quantitatively probe these memory mechanisms.

For much of 2016, it was hard to look at the news without seeing a headline about Zika. Images of parents holding newborn children with microcephaly grabbed the world’s attention and spurred the World Health Organization to make a rare declaration of a Public Health Emergency of International Concern (1). Despite widespread awareness of Zika and considerable will to contain its spread, data were scarce and initial predictions about Zika’s future were little more than conjectures loosely informed by historical statistics about the epidemiology of other diseases (2). A variety of issues continued to plague efforts to assess the threat posed by Zika, among them a high rate of asymptomatic infection, challenges associated with the interpretation of data on past exposure to Zika virus, and inconsistencies in case reporting (3). In PNAS, Zhang et al. (4) leverage the power of computational modeling to make the most of available data and offer new insights about what may have happened as Zika virus marched across the Americas. The power of the computational model developed by Zhang et al. (4) lies in its ability to tie together disparate empirical observations, each of which provides a glimpse into the spread of Zika virus but none of which tells the whole story. In a sense, this situation mirrors the parable of the blind men and the elephant. What Zhang et al. (4) have accomplished amounts to being provided with a description of an elephant’s trunk and tail and successfully predicting its tusks and ears. Such is the potential of a detailed computational model guided by a refined set of biological assumptions and informed with extensive data about factors deemed important by those assumptions. … [↵][1]1Email: taperkins{at}nd.edu. [1]: #xref-corresp-1-1