Neurosciences Commons^™

A Macaque Connectome For Large-Scale Network Simulations In Thevirtualbrain, Kelly Shen, Gleb Bezgin, Michael Schirner, Petra Ritter, Stefan Everling, Anthony R. Mcintosh

Brain and Mind Institute Researchers' Publications

© 2019, The Author(s). Models of large-scale brain networks that are informed by the underlying anatomical connectivity contribute to our understanding of the mapping between the structure of the brain and its dynamical function. Connectome-based modelling is a promising approach to a more comprehensive understanding of brain function across spatial and temporal scales, but it must be constrained by multi-scale empirical data from animal models. Here we describe the construction of a macaque (Macaca mulatta and Macaca fascicularis) connectome for whole-cortex simulations in TheVirtualBrain, an open-source simulation platform. We take advantage of available axonal tract-tracing datasets and enhance the existing …

Predator-Induced Fear Causes Ptsd-Like Changes In The Brains And Behaviour Of Wild Animals, Liana Y. Zanette, Emma C. Hobbs, Lauren E. Witterick, Scott A. Macdougall-Shackleton, Michael Clinchy

Brain and Mind Institute Researchers' Publications

© 2019, The Author(s). Predator-induced fear is both, one of the most common stressors employed in animal model studies of post-traumatic stress disorder (PTSD), and a major focus of research in ecology. There has been a growing discourse between these disciplines but no direct empirical linkage. We endeavoured to provide this empirical linkage by conducting experiments drawing upon the strengths of both disciplines. Exposure to a natural cue of predator danger (predator vocalizations), had enduring effects of at least 7 days duration involving both, a heightened sensitivity to predator danger (indicative of an enduring memory of fear), and elevated neuronal …

Consciousness-Specific Dynamic Interactions Of Brain Integration And Functional Diversity, Andrea I. Luppi, Michael M. Craig, Ioannis Pappas, Paola Finoia, Guy B. Williams, Judith Allanson, John D. Pickard, Adrian M. Owen, Lorina Naci, David K. Menon, Emmanuel A. Stamatakis

Brain and Mind Institute Researchers' Publications

Prominent theories of consciousness emphasise different aspects of neurobiology, such as the integration and diversity of information processing within the brain. Here, we combine graph theory and dynamic functional connectivity to compare resting-state functional MRI data from awake volunteers, propofol-anaesthetised volunteers, and patients with disorders of consciousness, in order to identify consciousness-specific patterns of brain function. We demonstrate that cortical networks are especially affected by loss of consciousness during temporal states of high integration, exhibiting reduced functional diversity and compromised informational capacity, whereas thalamo-cortical functional disconnections emerge during states of higher segregation. Spatially, posterior regions of the brain’s default mode …

Altered Motor, Anxiety-Related And Attentional Task Performance At Baseline Associate With Multiple Gene Copies Of The Vesicular Acetylcholine Transporter And Related Protein Overexpression In Chat::Cre+ Rats, Craig P. Mantanona, Johan Alsiö, Joanna L. Elson, Beth M. Fisher, Jeffrey W. Dalley, Timothy Bussey, Ilse S. Pienaar

Brain and Mind Institute Researchers' Publications

© 2019, The Author(s). Transgenic rodents expressing Cre recombinase cell specifically are used for exploring mechanisms regulating behavior, including those mediated by cholinergic signaling. However, it was recently reported that transgenic mice overexpressing a bacterial artificial chromosome containing choline acetyltransferase (ChAT) gene, for synthesizing the neurotransmitter acetylcholine, present with multiple vesicular acetylcholine transporter (VAChT) gene copies, resulting in altered cholinergic tone and accompanying behavioral abnormalities. Since ChAT::Cre+ rats, used increasingly for understanding the biological basis of CNS disorders, utilize the mouse ChAT promotor to control Cre recombinase expression, we assessed for similar genotypical and phenotypical differences in such rats compared …

Are Specific Learning Disorders Truly Specific, And Are They Disorders?, Lien Peters, Daniel Ansari

Brain and Mind Institute Researchers' Publications

© 2019 The Authors Specific learning disorders, such as dyslexia and dyscalculia, are frequently studied to inform our understanding of cognitive development, genetic mechanisms and brain function. In this Opinion Paper, we discuss limitations of this research approach, including the use of arbitrary criteria to select groups of children, heterogeneity within groups and overlap between domains of learning. By drawing on evidence from cognitive science, neuroscience and genetics, we propose an alternative, dimensional framework. We argue that we need to overcome the problems associated with a categorical approach by taking into account interacting factors at multiple levels of analysis that …

Functional Localization Of The Frontal Eye Fields In The Common Marmoset Using Microstimulation, Janahan Selvanayagam, Kevin D. Johnston, David J. Schaeffer, Lauren K. Hayrynen, Stefan Everling

Brain and Mind Institute Researchers' Publications

Copyright © 2019 the authors. The frontal eye field (FEF) is a critical region for the deployment of overt and covert spatial attention. Although investigations in the macaque continue to provide insight into the neural underpinnings of the FEF, due to its location within a sulcus, the macaque FEF is virtually inaccessible to electrophysiological techniques such as high-density and laminar recordings. With a largely lissencephalic cortex, the common marmoset (Callithrix jacchus) is a promising alternative primate model for studying FEF microcircuitry. Putative homologies have been established with the macaque FEF on the basis of cytoarchitecture and connectivity; however, physiological investigation …

Sign And Speech Share Partially Overlapping Conceptual Representations, Samuel Evans, Cathy J. Price, Jörn Diedrichsen, Eva Gutierrez-Sigut, Mairéad Macsweeney

Brain and Mind Institute Researchers' Publications

© 2019 The Author(s) Conceptual knowledge is fundamental to human cognition. Yet, the extent to which it is influenced by language is unclear. Studies of semantic processing show that similar neural patterns are evoked by the same concepts presented in different modalities (e.g., spoken words and pictures or text) [1–3]. This suggests that conceptual representations are “modality independent.” However, an alternative possibility is that the similarity reflects retrieval of common spoken language representations. Indeed, in hearing spoken language users, text and spoken language are co-dependent [4, 5], and pictures are encoded via visual and verbal routes [6]. A parallel approach …

Variational Representational Similarity Analysis, Karl J. Friston, Jörn Diedrichsen, Emma Holmes, Peter Zeidman

Brain and Mind Institute Researchers' Publications

© 2019 The Authors This technical note describes a variational or Bayesian implementation of representational similarity analysis (RSA) and pattern component modelling (PCM). It considers RSA and PCM as Bayesian model comparison procedures that assess the evidence for stimulus or condition-specific patterns of responses distributed over voxels or channels. On this view, one can use standard variational inference procedures to quantify the contributions of particular patterns to the data, by evaluating second-order parameters or hyperparameters. Crucially, this allows one to use parametric empirical Bayes (PEB) to infer which patterns are consistent among subjects. At the between-subject level, one can then …

Estimating Cognitive Workload In An Interactive Virtual Reality Environment Using Eeg, Christoph Tremmel, Christain Herff, Tetsuya Sato, Krzysztof Rechowicz, Yusuke Yamani, Dean J. Krusienski

Electrical & Computer Engineering Faculty Publications

With the recent surge of affordable, high-performance virtual reality (VR) headsets, there is unlimited potential for applications ranging from education, to training, to entertainment, to fitness and beyond. As these interfaces continue to evolve, passive user-state monitoring can play a key role in expanding the immersive VR experience, and tracking activity for user well-being. By recording physiological signals such as the electroencephalogram (EEG) during use of a VR device, the user's interactions in the virtual environment could be adapted in real-time based on the user's cognitive state. Current VR headsets provide a logical, convenient, and unobtrusive framework for mounting EEG …

A Sound-Sensitive Source Of Alpha Oscillations In Human Non-Primary Auditory Cortex, Alexander J. Billig, Björn Herrmann, Ariane E. Rhone, Phillip E. Gander, Kirill V. Nourski, Beau F. Snoad, Christopher K. Kovach, Hiroto Kawasaki, Matthew A. Howard, Ingrid S. Johnsrude

Brain and Mind Institute Researchers' Publications

Copyright © 2019 Billig, Herrmann et al. The functional organization of human auditory cortex can be probed by characterizing responses to various classes of sound at different anatomical locations. Along with histological studies this approach has revealed a primary field in posteromedial Heschl's gyrus (HG) with pronounced induced high-frequency (70-150 Hz) activity and short-latency responses that phase-lock to rapid transient sounds. Low-frequency neural oscillations are also relevant to stimulus processing and information flow, however, their distribution within auditory cortex has not been established. Alpha activity (7-14 Hz) in particular has been associated with processes that may differentially engage earlier versus …

An Accurate Registration Of The Bigbrain Dataset With The Mni Pd25 And Icbm152 Atlases., Yiming Xiao, Jonathan C Lau, Taylor Anderson, Jordan Dekraker, D Louis Collins, Terry Peters, Ali R Khan

Brain and Mind Institute Researchers' Publications

Brain atlases that encompass detailed anatomical or physiological features are instrumental in the research and surgical planning of various neurological conditions. Magnetic resonance imaging (MRI) has played important roles in neuro-image analysis while histological data remain crucial as a gold standard to guide and validate such analyses. With cellular-scale resolution, the BigBrain atlas offers 3D histology of a complete human brain, and is highly valuable to the research and clinical community. To bridge the insights at macro- and micro-levels, accurate mapping of BigBrain and established MRI brain atlases is necessary, but the existing registration is unsatisfactory. The described dataset includes …

A Framework For Evaluating Correspondence Between Brain Images Using Anatomical Fiducials., Jonathan C Lau, Andrew G Parrent, John Demarco, Geetika Gupta, Jason Kai, Olivia W Stanley, Tristan Kuehn, Patrick J Park, Kayla Ferko, Ali R Khan, Terry M Peters

Brain and Mind Institute Researchers' Publications

Accurate spatial correspondence between template and subject images is a crucial step in neuroimaging studies and clinical applications like stereotactic neurosurgery. In the absence of a robust quantitative approach, we sought to propose and validate a set of point landmarks, anatomical fiducials (AFIDs), that could be quickly, accurately, and reliably placed on magnetic resonance images of the human brain. Using several publicly available brain templates and individual participant datasets, novice users could be trained to place a set of 32 AFIDs with millimetric accuracy. Furthermore, the utility of the AFIDs protocol is demonstrated for evaluating subject-to-template and template-to-template registration. Specifically, …

Thirty-Five Years Of Computerized Cognitive Assessment Of Aging — Where Are We Now?, Avital Sternin, Alistair Burns, Adrian M. Owen

Brain and Mind Institute Researchers' Publications

Over the past 35 years, the proliferation of technology and the advent of the internet have resulted in many reliable and easy to administer batteries for assessing cognitive function. These approaches have great potential for affecting how the health care system monitors and screens for cognitive changes in the aging population. Here, we review these new technologies with a specific emphasis on what they offer over and above traditional ‘paper-and-pencil’ approaches to assessing cognitive function. Key advantages include fully automated administration and scoring, the interpretation of individual scores within the context of thousands of normative data points, the inclusion of …

Electroencephalographic Asymmetry, Emotion Regulation, And Their Relationships With Depression Risk, Aliza Jacob

Dissertations, Theses, and Capstone Projects

Background: Research investigating patterns of electroencephalographic (EEG) brain asymmetry aids our understanding of neural systems involved in the processing of emotion, motivation, and psychopathology. Withdrawal-motivated negative emotions characteristic of depression are associated with relative right prefrontal cortex (PFC) activity, whereas approach- motivated positive emotions are associated with relative left PFC activity. Styles of emotion regulation (ER), or modulation of the intensity and duration of emotional responses, are also associated with presence (e.g., suppression, or maladaptive ER) versus absence (e.g., cognitive reappraisal, or adaptive ER) of depression vulnerability. Most PFC asymmetry studies of emotion, depression, and/or ER rely upon EEG recorded …

Stimulus-Locked Responses On Human Upper Limb Muscles And Corrective Reaches Are Preferentially Evoked By Low Spatial Frequencies, Rebecca A. Kozak, Philipp Kreyenmeier, Chao Gu, Kevin Johnston, Brian D. Corneil

Brain and Mind Institute Researchers' Publications

© 2019 Kozak et al. In situations requiring immediate action, humans can generate visually-guided responses at remarkably short latencies. Here, to better understand the visual attributes that best evoke such rapid responses, we recorded upper limb muscle activity while participants performed visually-guided reaches towards Gabor patches composed of differing spatial frequencies (SFs). We studied reaches initiated from a stable posture (experiment 1, a static condition), or during on-line reach corrections to an abruptly displaced target (experiment 2, a dynamic condition). In both experiments, we detail the latency and prevalence of stimulus-locked responses (SLRs), which are brief bursts of EMG activity …

Binding During Sequence Learning Does Not Alter Cortical Representations Of Individual Actions, Patrick Beukema, Jörn Diedrichsen, Timothy D. Verstynen

Brain and Mind Institute Researchers' Publications

Copyright © 2019 the authors. As a sequence of movements is learned, serially ordered actions get bound together into sets to reduce computational complexity during planning and execution. Here, we investigated how actions become naturally bound over the course of learning and how this learning affects cortical representations of individual actions. Across 5 weeks of practice, neurologically healthy human subjects learned either a complex 32-item sequence of finger movements (trained group, n = 9; 3 female) or randomly ordered actions (control group, n = 9; 3 female). Over the course of practice, responses during sequence production in the trained group …

Cortical Beta Oscillations Are Associated With Motor Performance Following Visuomotor Learning, Svenja Espenhahn, Bernadette C.M. Van Wijk, Holly E. Rossiter, Archy O. De Berker, Nell D. Redman, Jane Rondina, Joern Diedrichsen, Nick S. Ward

Brain and Mind Institute Researchers' Publications

© 2019 The Authors People vary in their capacity to learn and retain new motor skills. Although the relationship between neuronal oscillations in the beta frequency range (15–30 Hz) and motor behaviour is well established, the electrophysiological mechanisms underlying individual differences in motor learning are incompletely understood. Here, we investigated the degree to which measures of resting and movement-related beta power from sensorimotor cortex account for inter-individual differences in motor learning behaviour in the young and elderly. Twenty young (18–30 years) and twenty elderly (62–77 years) healthy adults were trained on a novel wrist flexion/extension tracking task and subsequently retested …

Glucocorticoids And “Stress” Are Not Synonymous, Scott Macdougall-Shackleton

Brain and Mind Institute Researchers' Publications

Synopsis

Reference to glucocorticoids as “stress hormones” has been growing in prevalence in the literature, including in comparative and environmental endocrinology. Although glucocorticoids are elevated in response to a variety of stressors in vertebrate animals, the primary functions of glucocorticoids are not responding to stressors and they are only one component of complex suite of physiological and behavioral responses to stressors. Thus, the use of the short-hand phrase “stress hormone” can be misleading. Further, simply measuring glucocorticoids is not equivalent to measuring a stress response, nor is manipulating glucocorticoids equivalent to exposing an animal to a stressor. In this commentary …

Mapping Reward Values To Cues, Locations, And Objects: The Influence Of Reward Associations On Visual Attention, Constanza De Dios

USF Tampa Graduate Theses and Dissertations

Previous work has attempted to fit reward-driven attentional selection as being exogenous (stimulus-driven) or endogenous (goal-driven). However, recent work suggests that reward’s effects on attention depend on the type of stimulus feature that the motivational information is imparted during learning (incentive salience). If true, then reward should not be limited to solely impacting early perceptual or late categorization processes attention. The current study used event-related potentials (ERPs) to test the idea that reward’s effects on attention depend on the process that the reward information is embedded – early perceptual or late categorization. Results demonstrated reward-driven effects on perceptual representation when …

Understanding The Neural Bases Of Implicit And Statistical Learning, Laura J. Batterink, Ken A. Paller, Paul J. Reber

Brain and Mind Institute Researchers' Publications

© 2019 Cognitive Science Society, Inc. Both implicit learning and statistical learning focus on the ability of learners to pick up on patterns in the environment. It has been suggested that these two lines of research may be combined into a single construct of “implicit statistical learning.” However, by comparing the neural processes that give rise to implicit versus statistical learning, we may determine the extent to which these two learning paradigms do indeed describe the same core mechanisms. In this review, we describe current knowledge about neural mechanisms underlying both implicit learning and statistical learning, highlighting converging findings between …

Macaque Anterior Cingulate Cortex Deactivation Impairs Performance And Alters Lateral Prefrontal Oscillatory Activities In A Rule-Switching Task, Liya Ma, Jason L. Chan, Kevin Johnston, Stephen G. Lomber, Stefan Everling

Brain and Mind Institute Researchers' Publications

© 2019 Ma et al. In primates, both the dorsal anterior cingulate cortex (dACC) and the dorsolateral prefrontal cortex (dlPFC) are key regions of the frontoparietal cognitive control network. To study the role of the dACC and its communication with the dlPFC in cognitive control, we recorded local field potentials (LFPs) from the dlPFC before and during the reversible deactivation of the dACC, in macaque monkeys engaging in uncued switches between 2 stimulus-response rules, namely prosaccade and antisaccade. Cryogenic dACC deactivation impaired response accuracy during maintenance of—but not the initial switching to—the cognitively demanding antisaccade rule, which coincided with a …

Mouse Performance On A Novel Touchscreen Continuous Performance Task Is Dependent On Signaling In The Prelimbic Cortex, Tyler D. Dexter, Daniel Palmer, Amy C. Reichelt, Anita Taksokhan, Lisa M. Saksida, Tim J. Bussey

Western Research Forum

Attention is the cognitive processing that facilitates the ability to target and attend to relevant environmental stimuli, while filtering out irrelevant or distracting stimuli. Control over selective attention is theorized to be dependent on organized neural communication that stems from the medial prefrontal cortex (mPFC). To evaluate selective and sustained attention, mice were trained on the novel touchscreen rodent continuous performance task (rCPT), a task designed to emulate the human CPT. In the rodent version, images are continuously presented on a touchscreen, where mice have been trained to selectively respond to one image type while suppressing responses to all others. …

Competitive Frontoparietal Interactions Mediate Implicit Inferences, Martijn E. Wokke, Tony Ro

Publications and Research

Frequent experience with regularities in our environment allows us to use predictive information to guide our decision process. However, contingencies in our environment are not always explicitly present and sometimes need to be inferred. Heretofore, it remained unknown how predictive information guides decision-making when explicit knowledge is absent and how the brain shapes such implicit inferences. In the present experiment, 17 human participants (9 females) performed a discrimination task in which a target stimulus was preceded by a predictive cue. Critically, participants had no explicit knowledge that some of the cues signaled an upcoming target, allowing us to investigate how …

An Integration-To-Bound Model Of Decision-Making That Accounts For The Spectral Properties Of Neural Data, Ramón Guevara Erra, Marco Arbotto, Aaron Schurger

Psychology Faculty Articles and Research

Integration-to-bound models are among the most widely used models of perceptual decision-making due to their simplicity and power in accounting for behavioral and neurophysiological data. They involve temporal integration over an input signal (“evidence”) plus Gaussian white noise. However, brain data shows that noise in the brain is long-term correlated, with a spectral density of the form 1/fα (with typically 1 < α < 2), also known as pink noise or ‘1/f’ noise. Surprisingly, the adequacy of the spectral properties of drift-diffusion models to electrophysiological data has received little attention in the literature. Here we propose a model of accumulation of evidence for decision-making that takes into consideration the spectral properties of brain signals. We develop a generalization of the leaky stochastic accumulator model using a Langevin equation whose non-linear noise term allows for varying levels of autocorrelation in the time course of the decision variable. We derive this equation directly from magnetoencephalographic data recorded while subjects performed a spontaneous movement initiation task. We then propose a nonlinear model of accumulation of evidence that accounts for the ‘1/f’ spectral properties of brain signals, and the observed variability in the power spectral properties of brain signals. Furthermore, our model outperforms the standard drift-diffusion model at approximating the empirical waiting time distribution.

The Neural Association Between Arithmetic And Basic Numerical Processing Depends On Arithmetic Problem Size And Not Chronological Age, Anna A. Matejko, Daniel Ansari

Brain and Mind Institute Researchers' Publications

© 2019 The Authors The intraparietal sulcus (IPS) is thought to be an important region for basic number processing (e.g. symbol-quantity associations) and arithmetic (e.g. addition). Evidence for shared circuitry within the IPS is largely based on comparisons across studies, and little research has investigated number processing and arithmetic in the same individuals. It is also unclear how the neural overlap between number processing and arithmetic is influenced by age and arithmetic problem difficulty. This study investigated these unresolved questions by examining basic number processing (symbol-quantity matching) and arithmetic (addition) networks in 26 adults and 42 children. Number processing and …

Resonate: Reflections And Recommendations On Implicit Biases Within The Ismrm, Esther A.H. Warnert, Krishna Nayak, Ravi Menon, Curt Rice, John Port, Elizabeth A. Morris, Daniel K. Sodickson, Pia Sundgren, Karla L. Miller, Udunna C. Anazodo

Brain and Mind Institute Researchers' Publications

No abstract provided.

Simple Random-Interval Generation Reveals The Irresistibly Periodic Structure Of Perceived Time, Jessica A. Grahn, J. Eric Taylor

Brain and Mind Institute Researchers' Publications

Whole-integer ratios in musical rhythm are culturally universal. The reliable periodicity of rhythm inspired us to determine whether time perception, which is foundational to and inherently less structured than rhythm, is subject to similar biases. We created a random-interval generation task that exploits the nonrandom tendencies in perception and action in order to uncover the structural biases underlying temporal duration perception. Participants listened to and watched an audiovisual suprasecond temporal cue and were asked to subdivide it as randomly as possible in a prescribed number of responses. The results showed that the subdivision probability distributions were distinctly nonrandom, and closely …

Measuring Neural Time Series Data In A Sensory Deprivation Tank, Jackson Gregory, Tian Lan, Uri Maoz, Amir Raz

Student Scholar Symposium Abstracts and Posters

We are interested in studying the neurological and physiological effects of the float pod, also known as REST therapy, or sensory deprivation tank. Float pods rely on the concept of depriving most senses (from sound and light to temperature and proprioception) in a pool filled with buoyant salt water at body temperature. While float pods are most commonly used in spa environments, we intend to look at the potential benefits of floating under the empirical lens. In this study, we aim to measure neural activity using electroencephalography (EEG). We intend to look at the different levels of relaxation and the …

Does It Matter Whether You Or Your Brain Did It? An Empirical Investigation Of The Influence Of The Double Subject Fallacy On Moral Responsibility Judgments, Uri Maoz, Kellienne R. Sita, Jeroen J. A. Van Boxtel, Liad Mudrik

Psychology Faculty Articles and Research

Despite progress in cognitive neuroscience, we are still far from understanding the relations between the brain and the conscious self. We previously suggested that some neuroscientific texts that attempt to clarify these relations may in fact make them more difficult to understand. Such texts—ranging from popular science to high-impact scientific publications—position the brain and the conscious self as two independent, interacting subjects, capable of possessing opposite psychological states. We termed such writing ‘Double Subject Fallacy’ (DSF). We further suggested that such DSF language, besides being conceptually confusing and reflecting dualistic intuitions, might affect people’s conceptions of moral responsibility, lessening the …

A Consensus Guide To Capturing The Ability To Inhibit Actions And Impulsive Behaviors In The Stop-Signal Task., Frederick Verbruggen, Adam R Aron, Guido Ph Band, Christian Beste, Patrick G Bissett, Adam T Brockett, Joshua W Brown, Samuel R Chamberlain, Christopher D Chambers, Hans Colonius, Lorenza S Colzato, Brian D Corneil, James P Coxon, Annie Dupuis, Dawn M Eagle, Hugh Garavan, Ian Greenhouse, Andrew Heathcote, René J Huster, Sara Jahfari, J Leon Kenemans, Inge Leunissen, Chiang-Shan R Li, Gordon D Logan, Dora Matzke, Sharon Morein-Zamir, Aditya Murthy, Martin Paré, Russell A Poldrack, K Richard Ridderinkhof, Trevor W Robbins, Matthew Roesch, Katya Rubia, Russell J Schachar, Jeffrey D Schall, Ann-Kathrin Stock, Nicole C Swann, Katharine N Thakkar, Maurits W Van Der Molen, Luc Vermeylen, Matthijs Vink, Jan R Wessel, Robert Whelan, Bram B Zandbelt, C Nico Boehler

Brain and Mind Institute Researchers' Publications

Response inhibition is essential for navigating everyday life. Its derailment is considered integral to numerous neurological and psychiatric disorders, and more generally, to a wide range of behavioral and health problems. Response-inhibition efficiency furthermore correlates with treatment outcome in some of these conditions. The stop-signal task is an essential tool to determine how quickly response inhibition is implemented. Despite its apparent simplicity, there are many features (ranging from task design to data analysis) that vary across studies in ways that can easily compromise the validity of the obtained results. Our goal is to facilitate a more accurate use of the …