Individual neurons often produce highly variable responses over nominally identical trials, reflecting a mixture of intrinsic "noise" and systematic changes in the animal's cognitive and behavioral state. Disentangling these sources of variability is of great scientific interest in its own right, but it is also increasingly inescapable as neuroscientists aspire to study more complex and naturalistic animal behaviors. In these settings, behavioral actions never repeat themselves exactly and may rarely do so even approximately. Thus, new statistical methods that extract reliable features of neural activity using few, if any, repeated trials are needed. Accurate statistical modeling in this severely trial-limited regime is challenging, but still possible if simplifying structure in neural data can be exploited. We review recent works that have identified different forms of simplifying structure -- including shared gain modulations across neural subpopulations, temporal smoothness in neural firing rates, and correlations in responses across behavioral conditions -- and exploited them to reveal novel insights into the trial-by-trial operation of neural circuits.
It has been demonstrated that the statistical power of many neuroscience studies is very low, so that the results are unlikely to be robustly reproducible. How are neuroscientists and the journals in which they publish responding to this problem? Here I review the sample size justifications provided for all 15 papers published in one recent issue of the leading journal Nature Neuroscience. Of these, only one claimed it was adequately powered. The others mostly appealed to the sample sizes used in earlier studies, despite a lack of evidence that these earlier studies were adequately powered. Th…
When designing experimental studies with human participants, experimenters must decide how many trials each participant will complete, as well as how many participants to test. Most discussion of statistical power (the ability of a study design to detect an effect) has focussed on sample size, and assumed sufficient trials. Here we explore the influence of both factors on statistical power, represented as a two-dimensional plot on which iso-power contours can be visualised. We demonstrate the conditions under which the number of trials is particularly important, i.e. when the within-participan…
TRACE: Contrastive learning for multi-trial time-series data in neuroscience
Hertie Institute for AI in Brain Health, University of Tübingen（蒂耶脑健康人工智能研究所，蒂宾根大学）；Institute for Ophthalmic Research, University of Tübingen（眼科学研究 institute，蒂宾根大学）；Centre for Integrative Neuroscience, University of Tübingen（整合神经科学中心，蒂宾根大学）；Department of Neuroscience, Baylor College of Medicine（贝勒医学院神经科学系）；Center for Neuroscience and Artificial Intelligence, Baylor College of Medicine（贝勒医学院神经科学与人工智能中心）；Institute for Computer Science and Campus Institute Data Science, University of Göttingen（哥廷根大学计算机科学研究所与校园数据科学研究所）；Department of Ophthalmology, Byers Eye Institute, Stanford University School of Medicine（斯坦福大学医学院拜尔斯眼科研究所眼科系）；Stanford Bio-X, Stanford University（斯坦福大学生物-X项目，斯坦福大学）；Wu Tsai Neurosciences Institute, Stanford University（斯坦福大学吴氏神经科学研究所）；Department of Electrical Engineering, Stanford University（斯坦福大学电气工程系）
Neuroscientists frequently use a certain statistical reasoning to establish the existence of distinct neuronal processes in the brain. We show that this reasoning is flawed and that the large corresponding literature needs reconsideration. We illustrate the fallacy with a recent study that received an enormous press coverage because it concluded that humans detect deceit better if they use unconscious processes instead of conscious deliberations. The study was published under a new open-data policy that enabled us to reanalyze the data with more appropriate methods. We found that unconscious p…
Information theory is a practical and theoretical framework developed for the study of communication over noisy channels. Its probabilistic basis and capacity to relate statistical structure to function make it ideally suited for studying information flow in the nervous system. As a framework it has a number of useful properties: it provides a general measure sensitive to any relationship, not only linear effects; its quantities have meaningful units which in many cases allow direct comparison between different experiments; and it can be used to study how much information can be gained by obse…
Neuroimaging research has predominantly drawn conclusions based on classical statistics, including null-hypothesis testing, t-tests, and ANOVA. Throughout recent years, statistical learning methods enjoy increasing popularity, including cross-validation, pattern classification, and sparsity-inducing regression. These two methodological families used for neuroimaging data analysis can be viewed as two extremes of a continuum. Yet, they originated from different historical contexts, build on different theories, rest on different assumptions, evaluate different outcome metrics, and permit differe…
A common feature in many neuroscience datasets is the presence of hierarchical data structures, most commonly recording the activity of multiple neurons in multiple animals across multiple trials. Accordingly, the measurements constituting the dataset are not independent, even though the traditional statistical analyses often applied in such cases (e.g., Students t-test) treat them as such. The hierarchical bootstrap has been shown to be an effective tool to accurately analyze such data and while it has been used extensively in the statistical literature, its use is not widespread in neuroscie…
Information theory is a practical and theoretical framework developed for the study of communication over noisy channels. Its probabilistic basis and capacity to relate statistical structure to function make it ideally suited for studying information flow in the nervous system. It has a number of useful properties: it is a general measure sensitive to any relationship, not only linear effects; it has meaningful units which in many cases allow direct comparison between different experiments; and it can be used to study how much information can be gained by observing neural responses in single t…
Neuroscience is undergoing faster changes than ever before. Over 100 years our field qualitatively described and invasively manipulated single or few organisms to gain anatomical, physiological, and pharmacological insights. In the last 10 years neuroscience spawned quantitative big-sample datasets on microanatomy, synaptic connections, optogenetic brain-behavior assays, and high-level cognition. While growing data availability and information granularity have been amply discussed, we direct attention to a routinely neglected question: How will the unprecedented data richness shape data analys…
Many experimental paradigms in neuroscience involve driving the nervous system with periodic sensory stimuli. Neural signals recorded using a variety of techniques will then include phase-locked oscillations at the stimulation frequency. The analysis of such data often involves standard univariate statistics such as T-tests, conducted on the Fourier amplitude components (ignoring phase), either to test for the presence of a signal, or to compare signals across different conditions. However, the assumptions of these tests will sometimes be violated because amplitudes are not normally distribute…
Cross-frequency coupling (CFC) has been proposed to coordinate neural dynamics across spatial and temporal scales. Despite its potential relevance for understanding healthy and pathological brain function, the standard CFC analysis and physiological interpretation come with fundamental problems. For example, apparent CFC can appear because of spectral correlations due to common non-stationarities that may arise in the total absence of interactions between neural frequency components. To provide a road map towards an improved mechanistic understanding of CFC, we organize the available and poten…
Clarifying the conceptual dimensions of representation in neuroscience
New York University（纽约大学）；University of Washington（华盛顿大学）；University of Pennsylvania（宾夕法尼亚大学）；Boston University（波士顿大学）；INSERM, CEA, CNRS, Université Paris-Saclay（法国国家健康与医学研究院、法国原子能和替代能源委员会、法国国家科学研究中心、巴黎萨克雷大学）；GHU Paris psychiatrie et neuroscience, Sainte Anne Hospital（巴黎精神病学与神经科学医院集团、圣安娜医院）
How the brain processes information from external stimuli in order to perceive the world and act on it is one of the greatest questions in neuroscience. To address this question different time series analyzes techniques have been employed to characterize the statistical properties of brain signals during cognitive tasks. Typically response-specific processes are addressed by comparing the time course of average event-related potentials in different trials type. Here we analyze monkey Local Field Potentials data during visual pattern discrimination called Go/No-Go task in the light of informati…
CITS: Nonparametric Statistical Causal Modeling for High-Resolution Neural Time Series
University of California, San Francisco（旧金山加利福尼亚大学）；UCSF Weill Institute for Neurosciences（旧金山加利福尼亚大学威尔神经科学研究所）；Center for Research on Science and Consciousness（科学与意识研究中心）；National University of Singapore（新加坡国立大学）；Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco（旧金山加利福尼亚大学生物工程与治疗科学系）
The repeated presentation of an identical visual stimulus in the receptive field of a neuron may evoke different spiking patterns at each trial. Probabilistic methods are essential to understand the functional role of this variance within the neural activity. In that case, a Poisson process is the most common model of trial-to-trial variability. For a Poisson process, the variance of the spike count is constrained to be equal to the mean, irrespective of the duration of measurements. Numerous studies have shown that this relationship does not generally hold. Specifically, a majority of electro…
Synchronized brain rhythms, associated with diverse cognitive functions, have been observed in electrical recordings of brain activity. Neural synchronization may be well described by using the population-averaged global potential $V_G$ in computational neuroscience. The time-averaged fluctuation of $V_G$ plays the role of a "thermodynamic" order parameter $\cal {O}$ used for describing the synchrony-asynchrony transition in neural systems. Population spike synchronization may be well visualized in the raster plot of neural spikes. The degree of neural synchronization seen in the raster plot i…
Integrative neurocybernetic modeling in the era of large-scale neuroscience
Champalimaud Centre for the Unknown（Champalimaud 未知中心）；Janelia Research Campus（Janelia 研究campus）；Harvard University（哈佛大学）；Yale University（哥伦比亚大学）；École Polytechnique Fédérale de Lausanne (EPFL)（瑞士联邦理工学院）；RyvivyR Inc（RyvivyR 公司）
Columbia University Irving Medical Center（哥伦比亚大学欧文医学中心）
Inspired by the adaptation phenomenon of neuronal firing, we propose the regularity normalization (RN) as an unsupervised attention mechanism (UAM) which computes the statistical regularity in the implicit space of neural networks under the Minimum Description Length (MDL) principle. Treating the neural network optimization process as a partially observable model selection problem, the regularity normalization constrains the implicit space by a normalization factor, the universal code length. We compute this universal code incrementally across neural network layers and demonstrate the flexibil…
Recent experimental advances in neuroscience have opened new vistas into the immense complexity of neuronal networks. This proliferation of data challenges us on two parallel fronts. First, how can we form adequate theoretical frameworks for understanding how dynamical network processes cooperate across widely disparate spatiotemporal scales to solve important computational problems? And second, how can we extract meaningful models of neuronal systems from high dimensional datasets? To aid in these challenges, we give a pedagogical review of a collection of ideas and theoretical methods arisin…
Continuous attractors have been used to understand recent neuroscience experiments where persistent activity patterns encode internal representations of external attributes like head direction or spatial location. However, the conditions under which the emergent bump of neural activity in such networks can be manipulated by space and time-dependent external sensory or motor signals are not understood. Here, we find fundamental limits on how rapidly internal representations encoded along continuous attractors can be updated by an external signal. We apply these results to place cell networks to…
Information theory allows us to investigate information processing in neural systems in terms of information transfer, storage and modification. Especially the measure of information transfer, transfer entropy, has seen a dramatic surge of interest in neuroscience. Estimating transfer entropy from two processes requires the observation of multiple realizations of these processes to estimate associated probability density functions. To obtain these observations, available estimators assume stationarity of processes to allow pooling of observations over time. This assumption however, is a major …
