Simons Center for the Social Brain

SCSB Colloquium Series: Understanding Brain-Behavior Relationships
2023-09-13 16:00 - 17:00 UTC | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Wednesday, September 13, 2023
Location: 46-3002 (Singleton Auditorium) and YouTube Stream (https://youtube.com/live/-PbaB8cx8xQ)

Speaker: R. Todd Constable, Ph.D.
Affiliation: Elizabeth Mears and House Jameson Professor of Radiology and Bioimaging Sciences, Yale University School of Medicine
Host: Dr. Evelina Fedorenko

Talk title: Understanding Brain-Behavior Relationships
Abstract: This talk will explore the use of brain-behavior modeling in understanding brain organization. Focus will center on both aspects of such models. The first aspect is in terms of what the functional organization and how it reconfigures with performance across behavioral tasks tells us about brain organization across the lifespan and how it changes as a function of task. The second aspect is what such models tell us about novel and/or standardized behavioral paradigms that are commonly used. This second aspect will provide insight into the specific networks supporting performance on any given behavioral task and provide information on task combinations that better isolate specific cognitive constructs.

SCSB Lunch Series: Observational learning in the macaque brain
2023-09-08 12:00 - 13:00 UTC | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, September 8, 2023
Time: 12:00pm – 1:00pm
Location: SCSB Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/95884128103)
Speaker: Ruidong Chen, Ph.D.
Affiliation: Simons Postdoctoral Fellow, Mehrdad Jazayeri Laboratory, McGovern Institute, MIT
Talk title: Observational learning in the macaque brain
Abstract: Animals make inferences about latent causes from either their own actions and outcomes (experiential learning) or that of others (observational learning). Do animals discount the experience of others relative to their own, even when facing the same amount of external information? Are the neural substrates of experiential and observational learning shared, overlapping, or independent? To reveal and compare the neural mechanisms for belief updates from self-experience and social observations, we designed a two-player social learning task for both human and non-human primates (NHPs). Two NHPs perform this task with human-like behavior, where both actor and observer accumulate evidence over trials to make choices, with observers discounting evidence from actors relative to their own. I will report preliminary findings from ongoing neurophysiology experiments.

SCSB Lunch Series: Advanced Genetic Therapies for the Treatment of Rett Syndrome
2023-07-31 08:00 - 17:00 UTC | MA
Date: Friday, September 29, 2023
Time: 12:00pm – 1:00pm
Location: SCSB Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/92352928861)
Speaker: Chenjie Shen, Ph.D.
Affiliation: Postdoctoral Fellow, Guoping Feng Laboratory, McGovern Institute, MIT
Talk title: Advanced Genetic Therapies for the Treatment of Rett Syndrome
Abstract: Despite genome editing technologies have made unprecedented advances during the past decade, therapeutic use of genome editing in the CNS is still in its infancy. Rett syndrome is a neurodevelopmental disorder caused by genetic mutations in a X-linked gene named MECP2. The clinical progression of current gene replacement-based therapies encounters significant challenges owing to the dosage sensitivity of MeCP2. To overcome these challenges and facilitate the translation to human applications, 1). We explored various genetic therapeutic approaches for the most prevalent mutations found in RTT patients, including DNA/RNA base editing and sup-tRNA translational readthrough, aiming to restore MECP2 expression in vivo under its endogenous control. 2). We developed several MeCP2 humanized mouse models and generated iPSCs-derived human neurons to meticulously assess the effectiveness and safety of diverse genetic therapies. 3). We established a highly efficient genome editing method for generating knock in marmoset models that harbor human MeCP2 mutation, which will greatly facilitate study of primate-specific brain mechanisms in Rett Syndrome as well as testing and honing of various genetic therapies for effective genome editing and delivery of genetic medicine.

SCSB Lunch Series: Charactering the molecular architecture of excitatory synapse onto GABAergic interneurons
2023-05-19 12:00 - 13:00 UTC | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, May 19, 2023
Time: 12:00pm – 1:00pm
Location: SCSB Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/99475222915)
Speaker: Menglong Zeng, Ph.D.
Affiliation: Postdoctoral Fellow, Guoping Feng Laboratory, McGovern Institute, MIT
Talk title: Charactering the molecular architecture of excitatory synapse onto GABAergic interneurons
Abstract: Normal brain function requires a delicate balance between excitatory and inhibitory neurons. While only representing a small population of all neurons, GABAergic interneurons are essential to maintaining functional homeostasis across the brain. Genes encoding excitatory synaptic proteins tend to be one of the most prevalent hits in the screens of autism risk genes. However, the molecular architecture of excitatory synapses onto GABAergic interneurons has not been studied in sufficient details to establish the mechanistic insights needed to improve our understanding and treatment of autism.
In our study, we applied spatiotemporally precise proximity labeling techniques to uncover a novel assemblage of excitatory synaptic proteins onto parvalbumin interneurons. We discovered that parvalbumin interneurons have several strategies to distinguish their excitatory synapses molecularly and functionally from pyramidal neurons, possibly implicated in autism pathogenesis. We also combined gene editing, expansion microscopy and electrophysiology to study the structure and function of minority cell-type specific synapses within an intact circuit, to address the hypothesis that aberrant excitatory synaptic input onto interneurons contribute to neural circuit dysfunction in autism.

SCSB Colloquium Series: Development and neural diversity of septal nuclei
2023-05-10 16:00 - 17:00 UTC | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Wednesday, May 10, 2023
Location: 46-3002 (Singleton Auditorium) and YouTube Stream (https://youtu.be/WpLhcc2OOhE)
Speaker: Corey Harwell, Ph.D.
Affiliation: Associate Professor, Department of Neurology, Eli and Edythe Broad Center of Regeneration Medicine, UCSF
Host: Dr. Mriganka Sur
Talk title: Development and neural diversity of septal nuclei
Abstract: Septal nuclei in the basal forebrain have critical roles in regulating motivational and emotional states including fear, anxiety, and aggression. Dysfunction of septal neurons is believed to contribute to the pathophysiology of various psychiatric and behavioral disorders. The septum can be classified into two regions: the medial septum and the lateral septum. The medial septum is composed of cholinergic, GABAergic and glutamatergic neurons that primarily project to the hippocampus. While the lateral septum is made up of a diverse array of GABAergic projection neurons that have reciprocal connections with several brain regions known to regulate emotion, affect and motivational states. It is currently unclear how septal diversity and circuit wiring are specified during development. We have employed molecular genetic approaches and single-cell/nuclei RNA-seq to systematically assess the extent of septal cell diversity and the developmental logic for the production and wiring of these diverse neural cell types. We will discuss our recent progress in understanding the anatomical organization and functional specialization of neural cell types in the lateral septum.

SCSB Lunch Series: Conversation in the brain
2023-04-28 12:00 - 13:00 UTC | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
February 3, 2020 — McGovern Institute for Brain Research at MIT. Photo by Caitlin Cunningham Photography.
Date: Friday, April 28, 2023
Time: 12:00pm – 1:00pm
Location: SCSB Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/96362078147)
Speaker: Halie Olson, Ph.D.
Affiliation: Rebecca Saxe Laboratory, Department of Brain and Cognitive Sciences, MIT
Talk title: Conversation in the brain
Abstract: Elucidating how the brain processes language, especially during early development, is critical for understanding developmental disorders involving social communication such as autism. Beginning early in life, language is encountered and produced in complex, dynamic, and social contexts – and yet, neural measure typically study language in isolation. We developed a multimodal, child-friendly functional neuroimaging task to allow us to measure language-evoked activation in two contexts: (1) observing two people having a conversation, and (2) observing one person at a time speaking directly to the listener. We first validated this measure in adults, finding robust responses to comprehensible language in both contexts. Canonical language regions did not differentiate between the two contexts, but some theory of mind regions, as well as some right hemisphere homologues of language regions, did respond more strongly to dialogue. In ongoing work, we are using this measure in young children, both as a tool to measure language processing, and as a means to test how language is processed in different social contexts.

SCSB Colloquium Series: Rett syndrome: Are we on a path to a disease modifying treatment?
2023-04-19 16:00 - 17:00 UTC | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Wednesday, April 19, 2023
Location: 46-3002 (Singleton Auditorium) and YouTube Stream (https://youtu.be/mzG8H9WYRfc)
Speaker: Gail Mandel, Ph.D.
Affiliation: Senior Scientist, Vollum Institute, Oregon Health & Science University
Hosts: Dr. Guoping Feng and Dr. Chenjie Shen
Talk title: Rett syndrome: Are we on a path to a disease modifying treatment?
Abstract: I will present some new and promising data that points to targeted RNA editing as a potential means to repair and potentially reverse symptoms in a childhood neurological disease. The development of our approach has focused on Rett syndrome, a neurological disease that is caused by de novo loss of function mutations in the gene encoding the transcriptional repressor, Methyl CG binding protein 2 (MECP2). Rett syndrome mouse models are an excellent testing ground for the efficacy of a targeted RNA editing approach to repair mutations at the root source in neural cells. The disorder is specific to the nervous system, and early work has shown that Rett-like symptoms are reversible in mice following MeCP2 restoration at the postnatal symptomatic stage. Our recent findings will be discussed in the context of alleviating, in a new mouse model, a hallmark respiratory symptom that closely replicates the symptom in female Rett syndrome patients.

SCSB Colloquium Series: The Social Origins of Language and Thought
2023-04-05 16:00 - 17:00 (America/New_York) | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Wednesday, April 5, 2023
Location: 46-3002 (Singleton Auditorium) and YouTube Stream (https://youtu.be/B8gSpIoEpjQ)
Speaker: Robert Seyfarth, Ph.D.
Affiliation: Emeritus Professor of Psychology, University of Pennsylvania
Host: Dr. Ev Fedorenko
Talk title: The Social Origins of Language and Thought
Abstract: In humans, thought and language have evolved together. The same holds for monkeys and apes. Yet compared to humans, nonhuman primates present us with a dilemma: they have a relatively small repertoire of calls but live for years in complex societies where individuals use communication and cognition to establish and maintain their social relations. How do they manage? What do they know about the relations among their companions, and what does their social knowledge tell us about the origins of human language and thought?

SCSB Lunch Series: The consequence of dysfunctional mitochondria in Rett Syndrome astrocytes
2023-03-24 12:00 - 13:00 UTC | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, March 24, 2023
Time: 12:00pm – 1:00pm
Location: SCSB Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/92171523539)
Speaker: Danielle Tomasello, Ph.D.
Affiliation: Postdoctoral Fellow, Rudolf Jaenisch Laboratory, Whitehead Institute for Biomedical Research
Talk title: The consequence of dysfunctional mitochondria in Rett Syndrome astrocytes
Abstract: The brain requires an incredible amount of energy to function compared to other organs. In addition to roles in neurogenesis and synaptic growth and pruning, astrocytes supply essential metabolites and transfer their own mitochondria to neurons. This fundamental mechanism raises further questions on non-cell autonomous contribution of astrocytes in Rett Syndrome, a severe neurodevelopmental disorder. I will discuss how mutations in MECP2 impact mitochondrial dynamics and energy metabolism in human stem cell-derived astrocytes in 2D culture and 3D cerebral organoids. I will define the mechanisms behind mitochondrial deficits, and how transfer of these dysfunctional mitochondria impact neuronal activity. We do not fully understand the impact of MECP2 mutations on gene expression and chromatin landscapes in the human brain, and how MECP2 functions as the brain develops. To address these areas, I used a multiomics approach on Rett Syndrome cerebral organoids which uncovered novel findings into how MECP2 function greatly differs between neurons and glia in the developing human brain.

SCSB Colloquium Series: Flexible generalization in autism and language
2023-03-15 16:00 - 17:00 UTC | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Wednesday, March 15, 2023
Location: 46-3002 (Singleton Auditorium) and YouTube Stream (https://youtu.be/KFnyDlrab5w)
Speaker: Adele Goldberg, Ph.D.
Affiliation: Professor, Princeton University, Psychology Department, Programs in Linguistics, Cognitive Science, NLP
Host: Dr. Roger Levy
Talk title: Flexible generalization in autism and language
Abstract: Converging evidence from linguistics, psychology, and machine learning has led to a growing recognition that words and grammatical constructions are learned by flexibly categorizing over witnessed examples. This suggests a particular cognitive factor should impact the learning and use of language: skill in flexibly extending categories. Given prior findings that autistic individuals tend to display more veridical, less flexible categorization in the perceptual domain, we hypothesized that the same tendency in the cognitive domain would impact autistic individuals’ language. Two completed studies confirm that autistic children and adults underperform their neurotypical peers in language tasks that benefit from flexible meaning extension while performing comparably or better than the neurotypicals on related language tasks that did not require flexible categorization. The next step is to test an intervention aimed at jump-starting early word learning in young autistic children by drawing their attention to a particularly useful type of early meaning extension.

SCSB Colloquium Series: Memory, learning to learn, coordinated and discoordinated control of cognitive representations
2023-03-01 16:00 - 17:00 UTC | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Wednesday, March 1, 2023
Location: 46-3002 (Singleton Auditorium) and YouTube Stream (https://youtu.be/I98V_gZ4H2w)
Speaker: André Fenton, Ph.D.
Affiliation: Professor, and Director, Center for Neural Science, New York University
Host: Dr. Matthew Wilson
Talk title: Memory, learning to learn, coordinated and discoordinated control of cognitive representations
Abstract: Biological neural networks can represent information in the collective action potential discharge of neurons, and store that information amongst the synaptic connections between the neurons that both comprise the network and govern its function. The strength and organization of synaptic connections adjust during learning, but many cognitive neural systems are multifunctional, making it unclear how continuous activity alternates between the transient and discrete cognitive functions like encoding current information and recollecting past information, without changing the connections amongst the neurons. This lecture will summarize our investigations of mutant mice that model the genetic defect in Fragile X syndrome (FXS), the most common genetic cause of autism and intellectual disability. I then describe our investigations of the molecular and biochemical mechanisms that change synaptic function to persistently store spatial memory in the rodent hippocampus. I will then report on how entorhinal cortex-hippocampus circuit function changes during cognitive training that creates memory, as well as learning to learn in mice. I will describe how the hippocampus system operates like a competitive winner-take-all network, that, based on the dominance of its current inputs, self organizes into either the encoding or recollection information processing modes. We find no evidence that distinct cells are dedicated to those two distinct functions, rather activation of the hippocampus information processing mode is controlled by a subset of dentate spike events within the network of learning-modified, entorhinal-hippocampus excitatory and inhibitory synapses. I will close by reexamining the findings from the FXS mutant mouse.

SCSB Lunch Series: Child-directed listening: How adults understand what young children say
2023-02-24 12:00 - 13:00 UTC | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, February 24, 2023
Time: 12:00pm – 1:00pm
Location: SCSB Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/91754454830)

Speaker: Stephan Meylan, Ph.D.
Affiliation: Postdoctoral Associate, MIT Brain and Cognitive Sciences, Computational Psycholinguistics Lab
Talk title: Child-directed listening: How adults understand what young children say
Abstract: Research on child language acquisition has traditionally focused on children’s cognitive processes. However, early communication and coordination also depends on the cognitive processes of adult caregivers, as they must infer what children are trying to communicate even when children’s early speech differs substantially from adult speech. In this talk, I will show how a suite of hybrid Bayesian / neural network models of spoken word recognition can help us understand how adults do this. These models reveal that adults rely minimally on the acoustic signal produced by children, and instead heavily depend on prior beliefs about what children are likely to say, along with contextual cues. I’ll show some of the differences between adult word recognition of the speech of typically-developing children and the one child in the sample with an ASD diagnosis; finally, I’ll conclude by discussing the consequences of positing an inferentially-powerful adult listener for theories of first language acquisition.

SCSB Colloquium Series: Understanding somatosensory circuit alterations in autism spectrum disorder
2023-02-15 16:00 - 17:00 UTC | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Wednesday, February 15, 2023
Location: 46-3002 (Singleton Auditorium) and YouTube Stream (https://youtu.be/us4cepD9jPs)
Speaker: Lauren Orefice, Ph.D.
Affiliation: Assistant Professor, Massachusetts General Hospital / Harvard Medical School
Host: Dr. Polina Anikeeva
Talk title: Understanding somatosensory circuit alterations in autism spectrum disorder
Abstract: Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder, and surprisingly, the majority of individuals with ASD exhibit altered sensitivity to light touch. Our findings reveal that dysfunction of peripheral somatosensory neurons, not neurons in the brain, causes tactile over-reactivity in ASD models, and this tactile over-reactivity contributes to aberrant social behaviors in mice. We have found that some ASD-related behaviors can be improved with peripherally restricted pharmacological approaches in mouse models. I will present ongoing work about the mechanisms through which peripheral somatosensory neuron dysfunction leads to changes in cortical development, ultimately resulting in altered somatosensation and social behaviors.

SCSB Lunch Series: Temporal expectation in marmosets
2023-02-10 12:00 - 13:00 UTC | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, February 10, 2023
Time: 12:00pm – 1:00pm
Location: SCSB Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/93895393648)
Speaker: Shreya Mahajan
Affiliation: Mriganka Sur Laboratory, MIT
Host: Dr. Mriganka Sur
Talk title: Temporal expectation in marmosets
Abstract: Temporal expectation is the ability to use information from past events to predict their occurrence in the future, which allows the allocation of appropriate sensory resources in preparation for the event. Problems with time perception have been linked to several behavioral and cognitive impairments in individuals with autism spectrum disorders. We are investigating how the brain acquires temporal expectation, using a marmoset as an animal model. We trained freely behaving marmosets to perform a simple touchscreen-based timing task, and recorded reaction times and intracranial electroencephalogram (EEG) activity from 4 brain regions, as they were trained from a naïve state until they attained expertise. The behavioral change from the naïve state to the expert was well described with a hazard rate model. A trial by trial analysis of EEG data revealed a significant increment in EEG activity corresponding to anticipation of different events during the task, most prominently before reward delivery. These increments also noticeably changed across sessions as the animal acquired the temporal expectation model. Additionally, significant correlations were seen between the reaction times and the activities from the right parietal and the frontal regions during stimulus presentation period. Thus, the acquisition and representation of temporal expectation engages widespread cortical regions, with specific loci representing specific epochs of the task.

SCSB Colloquium Series: Michael Long, Ph.D.
2022-12-14 16:00 - 17:00 (America/New_York) | MA
Date: Wednesday, December 14, 2022
Location: 46-3002 (Singleton Auditorium) and YouTube Stream (https://youtu.be/HMZ3uy2r9GM)
Speaker: Michael A. Long, Ph.D.
Affiliation: Thomas and Suzanne Murphy Professor of Neuroscience, New York University School of Medicine
Host: Dr. Ev Fedorenko
Talk title: Neural mechanisms of interactive communication
Abstract: Vocal communication is central to our everyday lives, facilitating social exchange. Despite significant recent discoveries, the neural mechanisms underlying coordinated vocal exchanges remain poorly understood. We examine the brain processes involved in interactive vocal behaviors, focusing on forebrain circuitry in the human brain as well as a new rodent model for vocal communication. We identify brain activity in key regions in both species and demonstrate that these dynamics are critical for interactive vocalizations.

SCSB Lunch Series: Pawan Sinha, Ph.D.
2022-12-02 12:00 - 13:00 (America/New_York) | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, December 2, 2022
Time: 12:00pm – 1:00pm
Location: SCSB Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/98080251233)
Speakers: John Gabrieli, Grover Hermann Professor of Health Sciences and Technology and Cognitive Neuroscience, McGovern Institute, MIT;
Jesse Snedeker, Professor, Department of Psychology, Harvard University;
Pawan Sinha, Professor, Department of Brain and Cognitive Sciences, MIT
Host: Dr. Mriganka Sur
Talk title: Predictive Processes in Autistic and Neuro-typical Individuals

Abstract: Environmental uncertainty presents marked challenges for individuals with autism. Recent theoretical work suggests that autism may impact predictive skills, but empirical findings are mixed across a variety of tasks and participant samples. As part of an ongoing SCSB supported Targeted Project, we have undertaken a set of interlocking studies at MIT and Harvard that assess predictive skills across a broad range of perceptual, cognitive, and linguistic domains, employ behavioral as well as brain measures (EEG and fMRI), and are conducted with children and adults to allow for a developmental analysis of findings. We shall present an update on the results so far which point to a nuanced interpretation of the predictive challenge hypothesis, in contrast to a domain-general compromise of such processes.

SCSB Colloquium Series: Jun Huh, Ph.D.
2022-11-30 16:00 - 17:00 UTC | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Wednesday, November 30, 2022
Hybrid Location: 46-3002 (Singleton Auditorium) and YouTube stream (https://youtu.be/zB3Am6qoVts)
Speaker: Jun Huh, Ph.D.
Affiliation: Associate Professor of Immunology, Harvard Medical School
Host: Dr. Mriganka Sur
Talk title: Maternal gut bacteria dictate offspring’s neurodevelopmental and immune-primed phenotypes.
Abstract: Along with genetic factors, environmental factors are critical contributors to inflammatory disorders such as inflammatory bowel diseases (IBDs) and neurodevelopmental disorders such as autism. Gut microbes are one of these non-genetic factors that define a threshold to either maintaining a homeostatic balance or developing diseases. I will discuss our ongoing efforts to dissect maternal gut microbes’ effects on influencing offspring’s immune and neurodevelopmental phenotypes.

SCSB Lunch Series: Sophie Bridgers, Ph.D.
2022-11-18 12:00 - 13:00 (America/New_York) | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, November 18, 2022
Time: 12:00pm – 1:00pm
Location: SCSB Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/96889086712)
Speaker: Sophie Bridgers, Ph.D.
Affiliation: Simons Postdoctoral Fellow, Laura Schulz Laboratory, MIT
Host: Dr. Laura Schulz
Talk title: Loopholes: A window into goal communication and alignment
Abstract: Finding and exploiting loopholes, a possible but unintended interpretation of a rule or request, is a familiar facet of fable, law, and everyday life. A child may respond to their parent who says “It’s time to the put the tablet down” by continuing to play with the tablet after physically putting it down on the floor. Engaging with loopholes requires a nuanced understanding of goals, social ambiguity, and value alignment and offers a new lens through which to examine human communication and cooperation. However, cognitive and computational research on how humans learn to find these creative workarounds remains scarce. In this talk, I will first present a proposal for a formal framework of goal communication that supports intentional misunderstandings. Second, I will share a series of experiments with non-autistic children and adults that (1) reveal loophole behavior emerges around age five and is prevalent and diverse in parent-child and adult-adult interactions, and (2) indicate adults and children evaluate loopholes more leniently than outright non-compliance, as well as predict others exploit loopholes when goals are in conflict but there is a pressure to cooperate. I will also share ongoing work with autistic populations and conclude with a discussion of the development of loophole behavior. This work has implications for improving communication among humans, across developmental and neurodiverse populations, as well as for safer human-AI interactions.​​

SCSB Lunch Series: Kohitij Kar, Ph.D.
2022-11-04 12:00 - 13:00 UTC | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, November 4, 2022
Time: 12:00pm – 1:00pm
Location: SCSB Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/99707164021)
Speaker: Kohitij Kar, Ph.D.
Affiliation: Assistant Professor, Faculty of Science, York University (Toronto); Canada Research Chair in Visual Neuroscience; Visiting Scientist at McGovern Institute for Brain Research at MIT (DiCarlo Lab); Research Affiliate at the Center for Brain, Minds and Machines (MIT); Scientific Advisor, BeMe.ai
Host: Dr. Alan Jasanoff
Talk title: Developing a closed-loop framework using artificial neural networks and non-human primate experiments to test theories of atypical visual processing in autistic adults.
Abstract: Despite ample behavioral evidence of atypical sensory processing in autistic individuals, the neural underpinnings of such behavioral heterogeneities remain unclear. To probe these neural mechanisms, I will present our attempts to use a closed-loop framework using rhesus macaques and artificial neural network (ANN) models of the primate ventral visual pathways:

I will demonstrate how we can interchangeably test ANNs, macaques, and human subjects, on the same visual tasks that show behavioral differences in autistic adults.
I will demonstrate how we can generate ANN-based predictions for neurobehavioral markers of autism (related to these tasks) and conduct targeted neural measurements and brain perturbations in rhesus macaques to interrogate and test specific brain circuit related hypotheses.
I will present our first attempts to use ANN-driven approaches to generate more “diagnostic” image sets during human behavioral testing and image-pixel modification based novel behavioral modulation strategies.

SCSB Colloquium Series: Anne E. West, M.D., Ph.D.
2022-10-26 16:00 - 17:00 (America/New_York) | MA
Date: Wednesday, October 26, 2022
Hybrid Location: 46-3002 (Singleton Auditorium) and YouTube stream (https://youtu.be/MOpB8i9ItFw)
Speaker: Anne E. West, M.D., Ph.D.
Affiliation: Professor of Neurobiology, Duke University School of Medicine
Host: Dr. Steven Flavell
Talk title: From chromatin regulation to synapse development in autism and intellectual disability

Abstract: Chromatin-associated proteins are a major class of genes mutated in autism spectrum disorder (ASD) and intellectual disability (ID). These genetic data indicate the importance of gene regulation for brain development, however a significant challenge for the field is to determine how disruptions of chromatin regulators may converge on specific biological processes in developing neurons. We have shown there is extensive chromatin regulation in postmitotic neurons as they mature and form synapses, and we are working to address the hypothesis that ASD/ID mutations in chromatin regulators may act at this late stage of development to disrupt neuronal function. Rahman Syndrome (RMNS) is a rare, genetic form of ID caused by de novo heterozygous mutations in H1-4, which encodes the linker histone H1.4. All RMNS-associated mutations in H1-4 are small insertions or deletions that create a shared C-terminal frameshift. Genetic data indicate that the mutant protein functions in a dominant negative or neomorphic manner to lead to RMNS phenotypes, but the biochemical and cellular consequences of expressing RMNS mutant histone H1.4 are poorly understood. We have found that expressing RMNS mutant histone H1.4 in rat hippocampal neurons leads to the disruption of synaptic gene expression and neuronal firing. We are now undertaking a series of studies to determine when and where histone H1.4 is expressed in the brain during development as a way to understand how the RMNS mutations of H1.4 can lead to ID. As a histone, H1.4 is a direct component of chromatin; thus, studying how mutations in this gene impair neural development offers the opportunity to gain unique and specific biochemical insight into mechanisms of chromatin regulation in neurons.

SCSB Lunch Series: Seng Bum Michael Yoo, Ph.D.
2022-10-21 12:00 - 13:00 (America/New_York) | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, October 21, 2022
Time: 12:00pm – 1:00pm
Location: SCSB Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/99631032115)
Speaker: Seng Bum Michael Yoo, Ph.D.
Affiliation: Past Simons Postdoctoral Fellow, Mehrdad Jazayeri
Laboratory. Current position: Assistant Professor, Sungkyunkwan University
Host: Dr. Mehrdad Jazayeri
Talk title: Using network models to probe reduced sensitivity to others’ information in observation learning
Abstract: Observational learning is the ability to learn about hidden states of the environment through observing others’ actions and outcomes. Although behavioral and neural signatures of observational learning have been reported, a mechanistic understanding of its underlying neural computations is understudied. Here, we designed a two-player probability reversal-learning task in which both actor and observer need to track the covert change of the reward probability of the options. We find that, even after matching all the information available to each agent, both human and nonhuman primates still learn less from others’ actions and outcomes than their own. We devised a performance-optimized network model to address what types of constraints would bring such suboptimal behavior. Once the model includes independent noise for each agent’s outcome, the model accounted for others’ actions and outcomes to a lesser degree. In sum, the result suggests that asymmetric weights for the action and outcome information would underlie reduced efficacy of observation learning.

SCSB Colloquium Series: Kate O'Connor-Giles, Ph.D.
2022-10-12 16:00 - 17:00 (America/New_York) | MA
Date: Wednesday, October 12, 2022
Hybrid Location: 46-3002 (Singleton Auditorium) and YouTube stream (https://youtu.be/oIT6LYEPXDA)
Speaker: Kate O’Connor-Giles, Ph.D.
Affiliation: Provost’s Associate Professor of Brain Science, Carney Institute for Brain Science and Neuroscience Department, Brown University
Host: Dr. Troy Littleton
Talk title: Genes and their regulation in synapse formation and function
Abstract: Nervous system function requires the integration of diverse neuronal subtypes into the neural circuits that drive thought and behavior. Diverse neuronal fates are specified during development through genetic programs that are the subject of intense study. Despite extensive diversity, all neurons share key features such as chemical synapses. However, it remains largely unknown how gene expression is coordinated to regulate the development of synapses. Our data indicates that synaptic synaptic gene expression is positively and negatively regulated at the level of chromatin accessibility over development. I will present our identification of a gene regulatory network underlying coordinated synaptic gene expression and synapse formation.

SCSB Lunch Series: Sajal Sen, Ph.D.
2022-09-23 12:00 - 13:00 (America/New_York) | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, September 23, 2022
Time: 12:00pm – 1:00pm
Location: SCSB Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/93546956086)
Speaker: Sajal Sen, Ph.D.
Affiliation: Simons Fellow, Alan Jasanoff Laboratory, MIT
Host: Dr. Alan Jasanoff
Talk title: Probing Cholinesterase Activity In Autism Using Novel Multimodal MRI Contrast Agents
Abstract: Autism spectrum disorders (ASD) are a diverse family of neurodevelopmental conditions that lack any consistent biomarkers to date. Cholinesterase (ChE) enzymes, which lyse choline-based esters at cholinergic synapses, have been emerging as a potential therapeutic target in ASDs, and could serve as synapse-specific biomarkers for these disorders. However, probe technologies to correlate ChE activity and ASD are not yet available. Our ongoing research, therefore, seeks to design and validate novel ChE-sensitive MRI contrast agents to probe cholinergic phenotypes in ASD models, facilitate therapy development, and ultimately establish a non-invasive diagnostic tool for the clinical evaluation of autistic patients. Our imaging agent design is based on a previously validated molecular mechanism developed in the Jasanoff lab to detect brain enzyme activity in animal models. The new contrast agent uses a chemical framework that facilitates probing ChE activity via multimodal imaging including MRI and optical methods. This added feature will permit valuable integration of readouts obtained over a range of spatial scales, both in living subjects and postmortem tissue. In this colloquium, I will describe the synthesis and validation of pilot imaging probes in vitro, as well as initial in vivo results using a lead ChE-responsive compound. This work is thus yielding novel tools for autism research, with long-term potential for evaluating cholinergic function in human subjects.

SCSB Colloquium Series: Meng-Chuan Lai, M.D., Ph.D.
2022-09-14 16:00 - 17:00 (America/New_York) | MA
Date: Wednesday, September 14, 2022
Location: Hybrid: YouTube stream (https://youtu.be/rSX8CcS0RwY) and 46-3002, Singleton Auditorium
Speaker: Meng-Chuan Lai, M.D., Ph.D.
Affiliation: Staff Psychiatrist and Clinician Scientist, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (Canada); Associate Professor, Departments of Psychiatry and Psychology, and Institute of Medical Science, University of Toronto (Canada)
Host: Dr. Pawan Sinha
Talk title: Sex, gender, and autism: From clinical to basic sciences
Abstract: There is increasing awareness to the complex influences of sex-related and gender-related factors on the presentation and recognition of autism. This knowledge comes from lived experiences shared by autistic individuals and their families, psychological and clinical research, and epidemiological observations. With this, autism is increasingly recognized in girls, women, and gender diverse people. This line of research unveils how the understanding spanning from classical to nuanced phenotypes of autism contributes to the epistemic iteration of the concept of autism. Meanwhile, there are increasing better-powered biological studies on the heterogeneity of autism related to sex (but much less so on the roles of gender attributes), and on the etiological relations between sex-related (but much less so gender-related) mechanisms and developmental mechanisms of autism. By integrating these new developments, I will share reflections on knowledge gaps, clinical implications, and research directions to improve the wellbeing of autistic people across sexes and genders.

Click here to view selected papers

SCSB Colloquium Series: Julia Kaltschmidt, Ph.D.
2022-05-18 16:00 - 17:00 (America/New_York) | Zoom Webinar, Virtual, MA
Date: Wednesday, May 18, 2022
Location: Zoom Webinar – Registration Required
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Speaker: Julia Kaltschmidt, Ph.D.
Affiliation: Associate Professor of Neurosurgery; Stanford Neurosciences Institute Faculty Scholar; Firmenich Next Generation Faculty Scholar
Host: Dr. Polina Anikeeva
Talk title: Mapping the “second brain”: development and organization of the enteric nervous system
Abstract: The enteric nervous system (ENS) populates the gastrointestinal (GI) tract and controls GI function. In contrast to the central nervous system, macrostructure of the ENS has been largely overlooked. Here, we visually and computationally demonstrate that the ENS is organized in circumferential stripes that regionally differ in development and neuronal composition. This characterization provides a blueprint for future understanding of region-specific GI function and identifying ENS structural correlates of GI disorders.

SCSB Colloquium Series: Linda Richards, Ph.D.
2022-05-11 16:00 - 17:00 (America/New_York) | Zoom Webinar, Virtual, MA
Queensland Brain Institute, Brisbane on June 28, 2020. PHOTO / PATRICK HAMILTON
Date: May 11, 2022
Location: Zoom Webinar – Registration Required
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Speaker: Linda J. Richards, AO, FAA, FAHMS, Ph.D.
Affiliation: Edison Professor and Chair, Department of Neuroscience; Director, McDonnell Center for Cellular & Molecular Neurobiology, Washington University School of Medicine
Host: Dr. Mriganka Sur
Talk title: Etiology and impact of Corpus Callosum Dysgenesis
Abstract: The corpus callosum is the largest fiber tract in the brain and connects the two cerebral hemispheres in placental mammals. Corpus Callosum Dysgenesis (CCD) in humans occurs in around 1:4000 live births either in isolation or as part of more complex congenital syndromes. People with CCD often display a core cognitive syndrome which includes slowed cognitive processing, restricted processing of complex and novel tasks and limited interhemispheric transfer of sensory-motor information (Brown and Paul 2019). In this seminar I will discuss the underlying etiology of CCD and how glial populations, regulated by specific molecular pathways, are critical for remodeling the midline, providing a crucial substrate for the growth of callosal axons. Callosal axons that would otherwise have crossed the midline instead form ectopic ipsilateral projections known as Probst bundles. CCD causes rewiring of the remaining axonal pathways in the brain demonstrating that the brain is capable of a remarkable degree of long-range axonal plasticity. In addition to the molecular regulation of CCD, we hypothesize that activity-dependent mechanisms are also important for interhemispheric connectivity. To study these early mechanisms, we have established a new laboratory animal model, the fat-tailed dunnart, a small mouse-sized marsupial. Dunnart young develop in the pouch and are born at the equivalent of a 7-week gestation human or embryonic day 10 mouse, allowing us to study early brain development in vivo at stages equivalent to in utero stages in rodents and humans. I will discuss our latest results using this animal model and evidence of evolutionarily conserved patterns of activity in the developing brain.

SCSB Lunch Series: Emily Hueske, Ph.D.
2022-05-06 12:00 - 13:00 (America/New_York) | MA
Date: Friday, May 6, 2022
Time: 12:00pm – 1:00pm
Location: Zoom meeting – https://mit.zoom.us/j/94097435062
Speaker: Emily Hueske, Ph.D.
Affiliation: Research Scientist, Graybiel Laboratory, McGovern Institute for Brain Research, MIT
Talk title: Striosomal circuits underlying repetitive behaviors in ASD model
Abstract: Repetitive or stereotyped behaviors are a cardinal feature of autism spectrum disorder. The Graybiel lab is focused on trying to identify particular circuits in the cortico-striatal-dopaminergic system that might account for the anxiety and stereotypic behaviors exhibited by many individuals on the autism spectrum, with special focus on the striosomal compartment of striatum that directly innervates dopaminergic midbrain neurons. Our previous work demonstrated that the degree of stereotypic behaviors in rats, mice and squirrel monkeys correlates with striosomal predominant expression of cfos. We find evidence of the same in marmoset. We recently published a chemogenetic approach to modulating striosomal or matrix circuit activity, and we are testing the effects of striosomal inhibition in Shank3B KO mice using DeepLabCut- and B-SOID-based pose estimation. Shank3B KO mice show elevated stereotypic behaviors, and we are finding that chemogenetic inhibition of striosomal populations reduces these elevated stereotypies. In order to establish a translational approach to manipulating striosomes, we are capitalizing on our findings from recent snRNA-seq analyses to identify enhancer regions likely to allow targeting of expression to striosomal populations in mouse and marmoset without use of recombinase-based methods. This work would allow chemogenetic modulation of striosomal populations in marmoset models just as we have performed in Shank3B knockout mice.

SCSB Lunch Series: Chenjie Shen, Ph.D.
2022-04-22 12:00 - 13:00 (America/New_York) | MA
Date: Friday, April 22, 2022
Time: 12:00pm – 1:00pm
Location: Zoom meeting – https://mit.zoom.us/j/97743148391
Speaker: Chenjie Shen, Ph.D.
Affiliation: Simons Fellow, Guoping Feng Laboratory, McGovern Institute, MIT
Talk title: From Disease Modeling to Next-Generation Gene Therapy
Abstract: Heterozygous mutations in the X-linked MeCP2 gene cause the profound neurological disorder Rett syndrome (RTT). Currently, there are no FDA-approved medicines for RTT. The traditional RTT gene therapy approach based on gene replacement faces two key challenges in preclinical development: First, MeCP2 is dosage-sensitive, and its overexpression causes MeCP2 duplication syndrome. Therefore, the level of MeCP2 in each cell must be maintained within physiological limits. In addition, due to X chromosome inactivation, gene therapy in RTT females has to accommodate the fact that approximately 50% of cells are already expressing wild-type MeCP2. Our research focuses on developing the next-generation gene therapy approaches including RNA and DNA base editing to restore MeCP2 function under its endogenous regulation. Besides, we develop a high efficacy of genome editing method for generating the MeCP2 knock-in marmoset model that is promising for both mechanistic and translational studies.

SCSB Colloquium Series: Liuba Papeo, Ph.D.
2022-04-13 16:00 - 17:00 (America/New_York) | Zoom Webinar, Virtual, MA
Date: Wednesday, April 13, 2022
Location: Zoom Webinar – Registration Required
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Speaker: Liuba Papeo, Ph.D.
Affiliation: Principal Investigator of THEMPO, Institut des Sciences Cognitives “Marc Jeannerod”, UMR5229, Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (France)
Host: Dr. Ev Fedorenko
Talk title: Relation perception and the social function of vision
Abstract: Vision supports important aspects of social life. First, highly specialized visual mechanisms have evolved to process faces and bodies, conspecifics and other animals. But social life is made up of social entities as much as the relationships between these entities. The core social content is in fact relational. In a series of behavioral and neuroimaging studies, we show that perception is specialized for seeing socially relevant relationships. The results illustrate how the representation of social interaction emerges from object perception, through the analysis of the spatial relationships between multiple faces and bodies in visual scenes. Thus, visual perceptual mechanisms – and a network of visual brain areas – can give rise to the first rudimentary representation of social interaction based on the mere physical structure of input, before inferential processes kick in.
Bio
I am cognitive neuroscientist with a PhD in Neuroscience (International School for Advanced Studies, SISSA, Trieste, Italy). My PhD thesis addressed the role of sensory-motor processes in word understanding, using the study of lesions and behavior in brain-damaged patients, non-invasive brain stimulation (TMS) and functional neuroimaging (fMRI). The thesis received two prizes, from the Italian Association of Psychology and from SISSA (2011).
In 2011, I was awarded two European grants, a “Marie Curie International Outgoing Fellowship”, and a “Talents for an International House Fellowship Program”. I pursued the former, which funded three years of postdoc at the Department of Psychology of Harvard University. Here, in collaboration with Prof. Alfonso Caramazza and Alvaro Pascual-Leone, I studied the network dynamics supporting language and concepts. In 2014, I obtained a fellowship from the UPFellows Cofund Program of the University Pompeu Fabra of Barcelona and the European Research Council, for a three-years research program on the cognitive and neural mechanisms for action understanding, carried out at the University Pompeu Fabra of Barcelona.
I was recruited by the CNRS and joined the Institut des Sciences Cognitives “Marc Jeannerod” in 2016. In 2017, I obtained a European Research Council Starting grant and a Grant “Jeunes Chercheuses et Jeunes Chercheurs” of the french Agence Nationale de la Recherche. At the CNRS, I have developed a research program on the representation of relations, and established the research team “Cognitive neurodevelopment”, which today includes eight members between PhD students, postdocs and a research assistant. In 2019, our team was selected to join the new Laboratoire d’Excellence (LabEX) CORTEX of the University of Lyon. In December 2020, I received a Fyssen Foundation Research Grant for a project of categorization and word learning in full-term and preterm infants. In 2021, I was promoted to Directrice de Recherche (Full professore) at the CNRS.
As a researcher, I am committed to contributing to scientific advancements as well as to using my role and position to increase equality and inclusion. The latter goal is as important to me as the former.

SCSB Colloquium Series: Pamela Feliciano, Ph.D.
2022-03-30 16:00 - 17:00 (America/New_York) | Zoom Webinar, Virtual, MA
Date: Wednesday, March 30, 2022
Location: Zoom Webinar – Registration Required
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Speaker: Pamela Feliciano, Ph.D.
Affiliation: Scientific Director, SPARK (SPARKforAutism.org); Simons Foundation Autism Research Initiative (SFARI)
Host: Dr. Pawan Sinha
Talk title: SPARK: Gene discovery and return of genetic results in over 22,000 people with autism
Abstract: We have created a large longitudinal research cohort, SPARK (SPARKForAutism.org) to advance research on the genetic, behavioral, and clinical features associated with ASD. SPARK represents the largest ASD cohort in the world, with over 100,000 individuals with ASD enrolled. Despite the known heritable nature of autism spectrum disorder (ASD), studies have primarily identified risk genes with de novo variants (DNVs). To capture the full spectrum of ASD genetic risk, we performed a two-stage analysis of rare de novo and inherited coding variants in 42,607 ASD cases, including 35,130 new cases recruited online by SPARK. We identified 60 genes with exome-wide significance (p < 2.5e-6), including five new risk genes (NAV3, ITSN1, MARK2, SCAF1, and HNRNPUL2). The association of NAV3 with ASD risk is entirely driven by rare inherited LoFs variants, with an average relative risk of 4, consistent with moderate effect. ASD individuals with LoF variants in the four moderate risk genes (NAV3, ITSN1, SCAF1, and HNRNPUL2, n = 95) have less cognitive impairment compared to 129 ASD individuals with LoF variants in well-established, highly penetrant ASD risk genes (CHD8, SCN2A, ADNP, FOXP1, SHANK3) (59% vs. 88%, p= 1.9e-06). In this study, we identified rare LoF variants in new ASD risk genes with modest effect size that are not strongly associated with ID. This finding represents a difference in phenotypic association with ID compared with other well-established, highly penetrant ASD genes. Another tenet of SPARK is to form a partnership with participants and return research results to them. SPARK identified 1,711 (7.7%) ACMG likely pathogenic (LP) and pathogenic (P) variants in 22,166 people with ASD from a pre-defined list of high-confidence ASD risk genes and CNVs. The returnable genetic results were extremely heterogeneous and included variants in 231 genes, 133 CNVs and microdeletions ranging in size from 7.7 kb to 28 Mb and 5 chromosomal aneuploidies. The number of returnable results has changed over the course of the study as new risk genes for ASD and neurodevelopmental conditions have been identified: 37 percent of variants (632 variants in 177 genes) that currently meet LP/P ACMG criteria were previously variants of uncertain significance (VUS) at the start of the study in 2015. Reconsenting and retaining those participants and assessing how to include them in return of results for this large cohort has challenges, and methods SPARK has developed may be applicable to other large genomic cohorts.
