Professor of Biology, Center for Behavioral Neuroscience, American University. DEGREE (if applicable)

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1 NAME: OMB No and (Rev. 10/15 Approved Through 10/31/2018) BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors. Follow this format for each person. DO NOT EXCEED FIVE PAGES. Mark Laubach, PhD era COMMONS USER NAME: LAUBACH POSITION TITLE: EDUCATION/TRAINING Professor of Biology, Center for Behavioral Neuroscience, American University INSTITUTION AND LOCATION DEGREE (if applicable) Completion Date MM/YYYY FIELD OF STUDY Lafayette College, Easton, PA AB 05/1989 Biology & Chemistry Bryn Mawr College, Bryn Mawr, PA MA 05/1991 Experimental Psychology Wake Forest University, Winston-Salem, NC PhD 05/1997 Neuroscience Duke University, Durham, NC Postdoc 07/2001 Neuroscience A. Personal Statement My laboratory uses an integrated set of methods to study the role of the frontal cortex and basal ganglia in the control of goal-directed behavior. We are experienced in carrying out behavioral tests of cognitive and sensorimotor function and routinely use methods such as multi-electrode recordings, intra-cranial pharmacology, viral tract-tracing, optogenetics, and chemogenetics. In my teaching activities at American University (AU), I teach courses on (i) cellular neurophysiology, (ii) neuroscience methods, with a focus on cutting-edge methods supported by President Obama's BRAIN Initiative, (iii) computer-based methods for data analysis and hardware control and (iv) cognitive neuroscience from an animal research perspective. Undergraduates from AU's new Neuroscience major have participated in research in my lab and gone on to PhD programs and the postbac program at NIH. I also serve as director of AU's Behavior, Cognition, and Neuroscience PhD program and am advising two PhD students, both women, who are currently working towards their dissertations on the medial prefrontal cortex in my lab. (Their research would be supported with funds from this award.) In my previous position at the Yale School of Medicine, I trained PhD students who won awards for their research (Donald B. Lindsley Prize from SfN), obtained postdocs at top universities (e.g. Cambridge), and have established their own research labs. I also trained undergraduates who won awards for their scholarship and research (Rhodes Scholar) and went on to top graduate and medical schools. My current research program is directed at understanding the role of the medial frontal cortex (MFC, aka mpfc) in the adaptive control of behavior. We collaborated with a human research group and found that the same markers for adaptive control, i.e. the ability to improve performance based on previous outcomes, are expressed by the frontal cortices of rats and humans (Narayanan et al., 2013). This study helped establish rodents as a legitimate model for studying the neuronal basis of motivational and cognitive control. A related study found similar reward monitoring signals in a spatial working memory task (Horst and Laubach, 2012). These studies led to lab to focus on how rewards modulate MFC activity. Using a variable interval procedure, we presented water rewards to thirsty rats after unpredictable delays and found that the act of consuming the rewards itself activates MFC neurons and triggers 4-8 Hz theta rhythms phase locked to the rats lick cycle (Horst & Laubach, 2013). This study drove my lab to examine how sucrose rewards modulate MFC activity. We used reversible inactivation and intra-cortical pharmacological methods to establish that the MFC is crucial for animals to show that they like one reward compared to another (incentive contrast effects) (Parent et al., 2015a) and that the hunger hormone ghrelin acts in the MFC to enhance intake of high-value food options (Parent et al., 2015b). Most recently, we reported evidence for an encoding of the reward value of liquid sucrose rewards by lick-entrained neuronal activity in the MFC (Amarante et al., 2017).

2 Narayanan NS, Cavanagh JF, Frank MJ, Laubach M. Common medial frontal mechanisms of adaptive control in humans and rodents. Nat Neurosci Dec;16(12): PMID: ; PMC Horst NK, Laubach M. Working with memory: evidence for a role for the medial prefrontal cortex in performance monitoring during spatial delayed alternation. J Neurophysiol Dec;108(12): doi: /jn PMID: ; PMCID: PMC Horst NK, Laubach M. Reward-related activity in the medial prefrontal cortex is driven by consumption. Front Neurosci Apr 11;7:56. doi: /fnins PMID: ; PMCID: PMC Parent MA, Amarante LM, Liu B, Weikum D, Laubach M. The medial prefrontal cortex is crucial for the maintenance of persistent licking and the expression of incentive contrast. Front Integr Neurosci Mar 27;9:23. doi: /fnint PMID: ; PMCID: PMC Parent MA, Amarante LM, Swanson K, Laubach M. Cholinergic and ghrelinergic receptors and KCNQ channels in the medial PFC regulate the expression of palatability. Front Behav Neurosci Oct 26;9:284. doi: /fnbeh PMID: ; PMCID: PMC Amarante LA, Caetano MS, Laubach M. Medial frontal theta is entrained to rewarded actions. J Neuroscience, In Press. [Preprint at BioRxiv 2017/05/ ; doi: B. Positions and Honors Positions and Employment Postdoctoral Fellow, Department of Neurobiology, Duke University, Durham, NC Research Associate, Department of Neurobiology, Duke University, Durham, NC Assistant Fellow, John B. Pierce Laboratory, New Haven, CT Assistant Professor of Neurobiology, Yale University, New Haven, CT Principal Investigator, Swartz Initiative for Theoretical Neurobiology at Yale Associate Fellow, John B. Pierce Laboratory, New Haven, CT Associate Professor of Neurobiology, Yale University, New Haven, CT Associate Professor of Biology [tenured], American University, Washington, DC 2014 Member, Center for Behavioral Neuroscience, American University, Washington, DC 2016 Director, Behavior, Cognition, & Neuroscience Graduate Program, American University, Washington, DC 2016 Professor of Biology, American University, Washington, DC Other Experience and Professional Memberships 1991 Member, Society for Neuroscience and American Physiological Society 2002 American Federation for Aging, Young Investigator Research Award 2008 Organizer for mini-symposium at SfN-08: Functional interactions among multiple brain areas during flexible associative learning 2008 Associate Editor, Frontiers in Integrative Neuroscience 2009 Adviser to Nandakumar Narayanan, recipient of Donald B. Lindsley award from the Society for Neuroscience (best PhD dissertation in behavioral neuroscience) 2010, 2011 Program committee and chair of workshops at CoSyNe meeting, 2010 and Co-organizer (with Jeremy Seamans and David Euston) for 2 nd workshop on the Computational Properties of the Prefrontal Cortex (CPPC), Sep 10-12, 2010, Whistler, BC 2012 Faculty adviser for Benjamine Liu (Undergradute student at Yale), Rhodes Scholar 2013 Top reviewer award from the Journal of Neuroscience 2013 Co-organizer (with Jerome Sallet and Sebastien Bouret) for conference Motivational and Cognitive Control (MCC), Sep 24-26, 2013, Paris, France 2014 Co-organizer (with Jeremy Seamans and Geoff Schoenbaum) for 3 rd workshop on the Computational Properties of the Prefrontal Cortex (CPPC), Oct 3-5, 2014, Whistler, BC Guest editor for special issue of the Journal of Physiology Paris on Neural Mechanisms for the Adaptive Control of Behavior 2015 Co-organizer (with Jeremy Seamans and Bruno Averbeck) for 4 th workshop on the Computational Properties of the Prefrontal Cortex (CPPC), May 15-17, 2015, Washington, DC

3 2015 Associate Editor at the Journal of Neuroscience 2016 Organizing committee member for 5 th workshop on the Computational Properties of the Prefrontal Cortex (CPPC), Aug 29-31, 2016, Lyon, France Co-Organizer of OpenBehavior, with Alexxai Kravitz (NIDDK Intramural Program), a website for sharing designs for hardware and software used in behavioral neuroscience research: Scholar-Teacher of the Year, American University Professional Service: Peer Review Groups/Grant Study Sections 2008: ZRG1-IFCN (Special section for reviews of grants by members of the Cognitive Neuroscience (COG) and Learning & Memory (LAM) study sections), July : Activation Section, Neural Systems Cluster, NSF, October : Collaborative Research in Computational Neuroscience, NSF/NIH, March : Activation Section, Neural Systems Cluster, NSF, October : Collaborative Research in Computational Neuroscience, NSF/NIH, January : Activation Section, Neural Systems Cluster, NSF, April : Collaborative Research in Computational Neuroscience, NSF/NIH, March : Collaborative Research in Computational Neuroscience, NSF/NIH, March : Collaborative Research in Computational Neuroscience, NSF/NIH, March : ZRG1-F02B-D (Sensory and Motor Neuroscience, Cognition and Perception Fellowships), June, : SPC Study Section, October 2017 C. Contribution to Science Neurophysiology of learning: I completed my PhD and postdoctoral training in labs that developed methods for multi-electrode recording. My studies using these methods were inspired by some of the first in vivo singleunit recording studies done in the 1960s on the motor cortex by Ed Evarts and his colleagues at NIH. In my postdoc with Miguel Nicolelis at Duke, I set out to use the newly developed multi-electrode methods to examine learning-related changes in the motor cortex. Our study (Laubach et al., 2000) was the first multielectrode investigation of how ensembles of neurons change as naive animals learn to sustain an action over a delay period to obtain rewards. We found that an encoding of expected behavioral outcomes develops in the motor cortex with learning. When I established my own lab, I asked my first graduate student to continue with this line of work. He carried out several studies that are described in the next section. One of them examined the role of learning in the expression of a behavioral marker for the adaptive control of action, post-error slowing (Narayanan and Laubach, 2008). In parallel to these studies, another early student in my lab examined how learning new tasks changes neuronal activity in the striatum. One of these studies was the first to record from the striatum throughout the period required for rats to initially learn a stimulus-response reversal task (Kimchi and Laubach, 20009). Another of these studies (Kimchi et al., 2009) tested a prominent model of action-outcome learning using multi-electrode recordings in the medial and lateral striatum and found, in contrast to our expectations, that changes in the lateral striatum preceded those in the medial striatum. These studies helped establish standards for using quantitative methods to study neuronal correlates of behavior. Laubach M, Wessberg J, Nicolelis MA. Cortical ensemble activity increasingly predicts behavioural outcomes during learning of a motor task. Nature Jun 1;405(6786): PMID: Narayanan NS, Laubach M. Neuronal correlates of post-error slowing in the rat dorsomedial prefrontal cortex. J Neurophysiol Jul;100(1): PMID: Kimchi EY, Laubach M. The dorsomedial striatum reflects response bias during learning. J Neurosci Nov 25;29(47): PMID: Kimchi EY, Torregrossa MM, Taylor JR, Laubach M. Neuronal correlates of instrumental learning in the dorsal striatum. J Neurophysiol Jul;102(1): PMID: Neural mechanisms of adaptive control: When I started my own lab at the Yale School of Medicine, I wanted to better understand the learning-related changes in the motor cortex that we reported in the main paper from my postdoctoral research (Laubach et al., 2000). Several studies had been published in the late 1990s and early 2000s that reported that lesions in the mpfc impaired the ability of rats and humans to withhold premature responding in delayed response tasks. We decided to examine this issue using reversible

4 inactivation methods. Using a fluorescent form of muscimol, a GABA-A agonist that silences neuronal spike activity, we found that the mpfc is necessary for limiting premature responding in delayed response tasks (Narayanan and Laubach, 2006). Next, we combined reversible inactivations of the mpfc with multi-electrode recordings in the motor cortex and found that mpfc activity regulates delay period firing and is necessary for the expression of outcome coding by neurons in the motor cortex (Narayanan and Laubach, 2006). We also recorded neuronal activity in the mpfc in the 2006 study, and found many neurons that fired persistently as rats waited to respond at the end of the delay period (similar to classic studies in the same cortical area in primates by Niki). The firing rates of these neurons could be used to predict when a mistake would be made before the rats made the mistakes. We now call this form of neuronal activity "prospective error encoding". In a related study, (Narayanan and Laubach, 2008; cited above) we found that a second form of outcome encoding occurred in the mpfc: neurons that became persistently active after mistakes were signaled. These cells fired until the animal next performed the task correctly and were correlated with the expression of post-error slowing in the behavioral session. Around this time, I applied multivariate statistical methods to these data sets and found two population-level signals associated with the initiation of the timed action and the passage of time while the action was sustained (Narayanan and Laubach, 2009). The neuronal signals were accompanied by major changes in simultaneously recorded field potentials. Most prominent was a persisting theta rhythm that occured when rats made mistakes. This signal was similar to several recent EEG studies of the human mpfc, e.g. by Jim Cavanagh and colleagues. I contacted Jim and asked him and his postdoc mentor, Michael Frank, to collaborate with us on a cross-species study. Our study tested human participants in the same task used for testing rodents in my lab. We found the same markers of adaptive control in the two species, and both were associated with post-error changes in response times. As above, these studies have been well cited, received media coverage (e.g. Nature NeuroPod), and led to my first graduate student, Nandakumar Narayanan, receiving the Lindsley Prize from SfN. Laubach et al., (2015) reviewed these studies and related computational modeling, and reported previously unpublished data on the role of temporal uncertainty in simple reaction-time performance and related neuronal signaling in the mpfc. Laubach M, Caetano MS, Narayanan NS. Mistakes were made: neural mechanisms for the adaptive control of action initiation by the medial prefrontal cortex. J Physiol Paris. 2015;109(1-3): PMID: Narayanan NS, Laubach M. Top-down control of motor cortex ensembles by dorsomedial prefrontal cortex. Neuron Dec 7;52(5): PubMed PMID: Narayanan NS, Laubach M. Delay activity in rodent frontal cortex during a simple reaction time task. J Neurophysiol Jun;101(6): PMID: ; PMC Narayanan NS, Cavanagh JF, Frank MJ, Laubach M. Common medial frontal mechanisms of adaptive control in humans and rodents. Nat Neurosci Dec;16(12): PMID: Statistical analysis of neurophysiological data: A major technical theme of my training and research has been the application of statistical methods to the analysis of behavioral and neurophysiological data. During my graduate training, in the early 1990s, I took classes in multivariate statistics and learned to use programs such as Matlab and R. Later, I developed applications of emerging methods such as independent component analysis (Laubach et al., 1999) for detecting correlations among groups of simultaneously recorded neurons and wavelet analysis (Laubach, 2004) for decoding behavioral outcomes based on temporal patterns in spike activity. These methods were featured in the primary paper from my postdoctoral research (Laubach et al., Nature, 2000; cited above) and in the first experimental studies on the motor cortex (Narayanan et al., 2005) and striatum (Kimchi and Laubach, 2009) that were published by my own lab. Laubach M, Shuler M, Nicolelis MA. Independent component analyses for quantifying neuronal ensemble interactions. J Neurosci Methods Dec 15;94(1): PMID: Laubach M. Wavelet-based processing of neuronal spike trains prior to discriminant analysis. J Neurosci Methods Apr 30;134(2): PMID: Narayanan NS, Kimchi EY, Laubach M. Redundancy and synergy of neuronal ensembles in motor cortex. J Neurosci Apr 27;25(17): PMID:

5 Kimchi EY, Laubach M. Dynamic encoding of action selection by the medial striatum. J Neurosci Mar 11;29(10): PMID: ; PMC Methods for perturbing neural function: Another technical theme of my research has been the development of methods for perturbing neural activity that allow for visualizing the anatomical extent of the manipulations and combining these methods with multi-electrode recordings. My lab was the first to use fluorescent muscimol for reversible inactivation studies (Narayanan et al., 2006). Through collaboration with a slice physiology lab, we later published a methods paper reporting how the drug works (Allen et al., 2008) and have shared our protocol for fluorescent muscimol with more than 50 labs worldwide. Most recently, we implemented optogenetics methods into our work (Parent et al., 2015), using low-cost high-power LEDs from Prizmatix, and have openly shared our methods with other labs interested in using these methods. Narayanan NS, Horst NK, Laubach M. Reversible inactivations of rat medial prefrontal cortex impair the ability to wait for a stimulus. Neuroscience. 2006;139(3): PMID: Narayanan NS, Laubach M. Top-down control of motor cortex ensembles by dorsomedial prefrontal cortex. Neuron Dec 7;52(5): PMID: Allen TA, Narayanan NS, Kholodar-Smith DB, Zhao Y, Laubach M, Brown TH. Imaging the spread of reversible brain inactivations using fluorescent muscimol. J Neurosci Methods Jun 15;171(1):30-8. PMID: Parent MA, Amarante LM, Liu B, Weikum D, Laubach M. The medial prefrontal cortex is crucial for the maintenance of persistent licking and the expression of incentive contrast. Front Integr Neurosci Mar 27;9:23. PMID: Full list of published work: