Simons Center for the Social Brain

SCSB Lunch Series with Dr. Lace Riggs: Anteromedial thalamocortical communication: Unexpected roles in affective cognition
2024-10-11 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 11, 2024
Time: 12:00pm – 1:00pm
Location: Simons Center Conference room 46-6011 + Zoom [https://mit.zoom.us/j/98067736560]
Speaker: Lace Riggs, Ph.D.
Affiliation: Simons Postdoctoral Fellow, Guoping Feng Lab, McGovern Institute for Brain Research at MIT and Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard
Talk title: Anteromedial thalamocortical communication: Unexpected roles in affective cognition
Abstract: Thalamocortical circuit dysfunction is implicated in the pathophysiology of neurodevelopmental conditions like autism. However, an outstanding question is how the thalamus regulates complex emotional and cognitive processes through its extensive corticolimbic projections. In this talk, I will show how the anteromedial nucleus of the thalamus (AM) can serve as a model substrate to understand the role of higher order thalamocortical circuits in both health and disease. While the function of AM is largely unknown, it is the major thalamic projection to the cingulate cortex, which is a subregion of the prefrontal cortex that is highly implicated in the social, emotional, and cognitive aspects of autism. I find that AM constrains cingulate activity through strong disynaptic feedforward inhibition and can dynamically shift cingulate activity toward hyperexcitability in response to aversive stimuli, altering the course of conflict-based decision-making. By forming reciprocal monosynaptic connections exclusively with the cingulate cortex, AM is able to serve a unique role in regulating affective cognition. Ongoing studies aim to provide novel insight into how affective states govern higher-order cognitive processes by examining cell-type specific mechanisms of thalamocortical dysfunction in preclinical models of autism.

SCSB Lunch Series: Toward an understanding of how the cerebello-thalamocortical pathway supports cognition [Gabriel Stine, Ph.D.]
2024-09-27 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 27, 2024
Time: 12:00pm – 1:00pm
Location: Simons Center Conference room 46-6011 + Zoom [https://mit.zoom.us/j/95345061608]
Speaker: Gabriel Stine, Ph.D.
Affiliation: Simons Postdoctoral Fellow, Jazayeri Lab, McGovern Institute for Brain Research, MIT
Talk title: Toward an understanding of how the cerebello-thalamocortical pathway supports cognition
Abstract: Mounting evidence suggests the cerebellum plays a critical role in cognitive function, and cerebellar abnormalities are common in individuals with autism spectrum disorder (ASD). In motor control, the cerebellum enables smooth, coordinated, and adaptable movements by forming internal models that predict the sensory consequences of actions, which are used to quickly correct errors and adapt to changes in the environment. An intriguing hypothesis is that the cerebellum plays a similar role in cognitive function, facilitating smooth, coordinated, and adaptable thought processes. In this talk, I will present our ongoing efforts to test this hypothesis in macaque monkeys. We developed a timing adaptation task in which subjects must predict the timing of events in the environment and use these predictions to improve and adapt their internal timekeeping. We are conducting large-scale, simultaneous recordings in the cerebello-thalamocortical pathway as monkeys perform this task. I will present preliminary findings that suggest the cerebellum plays an important role in modulating the monkey’s internal timekeeping based on prediction errors. Ultimately, we hope to develop a computational and circuit-level understanding of how the cerebellum supports cognitive function and generate new hypotheses about how this process is altered in ASD.

SCSB Lunch Series: From words to worlds: bridging language and thought for language-informed thinking
2024-09-13 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 13, 2024
Time: 12:00pm – 1:00pm
Location: Simons Center Conference room 46-6011 + Zoom [https://mit.zoom.us/j/93456739273]
Speaker: Lio Wong, Ph.D.
Affiliation: MIT Postdoctoral Researcher, Tenenbaum Lab, BCS, MIT
Talk title: From words to worlds: bridging language and thought for language-informed thinking
Abstract: What do we understand when we understand language? Human language offers a broad window into the landscape of our thoughts. We talk about what we see, believe, and imagine, posing questions and communicating our plans. Language, in turn, stocks our mental inventories with new concepts and theories, communicating ideas that we might not otherwise have discovered by thinking on our own even over the course of a lifetime. How do we make meaning from language, and how, in turn, does the meaning we construct from language draw on the other resources and capacities of human thought, from perception, to mental simulation and decision making? In this talk, I’ll overview an overarching framework, Rational Meaning Construction, which proposes how natural language can construct arbitrary expressions in a flexible, symbolic, and probabilistic language of thought that supports general inferences. I present examples and experiments demonstrating the range of this theory, modeling how concrete propositions and questions in language can update and query beliefs about the physical and social world. I’ll then present newer work showing how the same framework can be used to construct and propose world models from scratch that can be used to make sense of new language, and to relate language to decision making and planning.

SCSB Colloquium Series: Nancy Padilla-Coreano, Ph.D.
2024-09-11 16:00 - 17:00 (America/New_York) | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Wednesday, September 11, 2024
Location: 46-3002 (Singleton Auditorium)
Speaker: Nancy Padilla-Coreano, Ph.D.
Affiliation: Assistant Professor, Department of Neuroscience, University of Florida
Host: Dr. Steve Flavell
Talk title: Neural dynamics of social competence
Abstract: Most social species, from insects to humans, organize into social dominance hierarchies to decrease aggression, conserve energy, and maximize survival for the group. Despite how critical social and dominance behaviors are for successful interactions with other group members, it is unclear how the brain encodes social rank. The medial prefrontal cortex (mPFC) has been implicated in social dominance expression in rodents, and in social rank learning in humans. In this talk we uncover how the mPFC encodes social competition at the cell, circuit and network levels in mice.

SCSB Colloquium Series: Experiencing and understanding prosocial motivations in infancy and early childhood [Lindsey Powell, Ph.D.]
2024-05-22 16:00 - 17:00 UTC | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Wednesday, May 22, 2024
Location: 46-3002 (Singleton Auditorium)
Speaker: Lindsey Powell, Ph.D.
Affiliation: Assistant Professor, Department of Psychology, University of California San Diego
Host: Dr. Rebecca Saxe
Talk title: Experiencing and understanding prosocial motivations in infancy and early childhood
Abstract: Human prosociality is critical for both individuals and societies to thrive. In the first two years of life, infants begin both to engage in prosocial behavior and to recognize and evaluate the prosocial actions of others. In the first part of the talk, I will describe an fNIRS study investigating the neural correlates of helping behavior in 14- to 20-month-old toddlers. We find that responses in brain regions associated with adult feelings of empathic concern and distress (MPFC, SII), measured while participants watch videos of an actor in mild distress, are correlated with toddlers’ helping behavior. In the second part of the talk, I will describe a series of studies aimed at investigating how infants and children reason about others’ prosocial motivations, with a focus on their representations of affiliative relationships.

SCSB Lunch Series: Role of FMRP interactions with presynaptic ion channels in Fragile X Syndrome
2024-05-10 12:00 - 13:00 UTC | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, May 10, 2024
Time: 12:00pm – 1:00pm
Location: Simons Center Conference room 46-6011 + Zoom Meeting: https://mit.zoom.us/j/91647033337
Speaker: Chhavi Sood, Ph.D.
Affiliation: Simons Postdoctoral Fellow, Littleton Lab, Picower Institute, BCS, Department of Biology, MIT
Talk title: Role of FMRP interactions with presynaptic ion channels in Fragile X Syndrome
Abstract: Synaptic vesicle (SV) fusion occurs in response to Ca2+ influx from voltage-gated Ca2+ channels (VGCCs) at AZs. Multiple conserved proteins cluster SVs and VGCCs at the AZs. Additionally, BK channels (Ca2+-activated K+ channels) also cluster at AZs to rapidly repolarize the presynaptic membrane, close VGCCs, and terminate Ca2+ influx and SV release. Using the Drosophila model of Fragile X Syndrome (FXS) and neuromuscular junction, I aim to determine how FMRP controls VGCC and BK channel synaptic delivery and AZ abundance and how dysregulation of these interactions contributes to synaptic defects in FXS.

SCSB Lunch Series: Neural oscillation and sensory prediction in children with autism
2024-04-26 12:00 - 13:00 UTC | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, April 26, 2024
Time: 12:00pm – 1:00pm
Location: Simons Center Conference room 46-6011 + Zoom Meeting: https://mit.zoom.us/j/92247387492
Speaker: Winko An, Ph.D.
Affiliation: Postdoctoral Research Fellow, Boston Children’s Hospital/Harvard Medical School
Talk title: Neural oscillation and sensory prediction in children with autism
Abstract: The brain’s ability to automatically predict sensory information is key to perception. Predicted inputs are attenuated, while unexpected inputs are amplified and processed. Alteration in this “predictive coding” mechanism may contribute to autism characteristics, such as increased prediction errors and hypersensitivity, and is hypothesized to be associated with the imbalance between alpha/beta and gamma oscillations in brain signals. I will present a new study aimed at testing this hypothesis using EEG recordings from three groups of participants with different degrees of functional impairment – children with typical development, autism, and Phelan-McDermid syndrome. Preliminary findings on oscillatory power and neural response to oddballs among these groups will be shared.

SCSB Colloquium: Understanding and conquering pain [Clifford Woolf, M.B., B.Ch., Ph.D.,]
2024-04-24 16:00 - 17:00 UTC | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Wednesday, April 24, 2024
Location: 46-3002 (Singleton Auditorium). Please note this event will take place in person only
Speaker: Clifford Woolf, M.B., B.Ch., Ph.D.
Affiliation: Professor of Neurology and Neurobiology/Director of FM Kirby Neurobiology Center, Boston Children’s Hospital and Harvard Medical School
Talk title: Understanding and conquering pain
Abstract: Pain is one of the major challenges of contemporary medicine in terms of its high incidence, persistence in many patients, and the poor efficacy and adverse effects of most analgesics, as well as the contribution of prescription opioids to the opioid crisis. I would like to share our approach to studying the mechanisms of physiological and pathological pain both in preclinical rodent models using chronic nociceptive circuit recordings and a machine-learning based interrogation of pain-related behavior, and by studying human pain in a dish with iPSC-derived neurons, as well as a platform we have put together for identifying novel analgesics without an abuse liability.
Bio: Dr. Clifford J. Woolf was born in South Africa, where he earned his MB, BCh, and Ph.D. degrees. He then moved to London and became Professor of Neurobiology at University College London. In 1997 he was recruited by the Massachusetts General Hospital and Harvard Medical School to serve as the Richard J. Kitz Professor of Anesthesiology Research and director of the Neural Plasticity Research Group. In 2010 he was named director of the F. M. Kirby Neurobiology Center at Boston Children’s Hospital and became Professor of Neurology and Neurobiology at HMS. He is faculty both in the department of Neurobiology at Harvard Medical School and in the Harvard Stem Cell Institute. In 2022 he was appointed the Blackfan-Diamond Chair of Neuroscience Research at Boston Children’s. In 2020 Dr. Woolf was elected a fellow of the American Academy of Arts and Sciences and was awarded a Doctoris Honoris Causa from the University of Lausanne, Switzerland, he received a Gill Distinguished Scientist award and the Reeve-Irvine medal in 2017, and in 2015, the Kerr award from the American Pain Society. He has published over 320 research papers on molecular, cellular, and systems neurobiology and has 35 issued patents. He has an h-index of 166 and 124,000 citations. His research is devoted to investigating how the functional, chemical, and structural plasticity of neurons is involved in both the normal adaptive functions of the nervous system and in maladaptive changes that contribute to neurological diseases, with a particular focus on pain, regeneration, and neurodegeneration and on the exploitation of stem cell derived neurons to model disease and for drug screening. Dr. Woolf has founded several companies and is a consultant and SAB member for several pharmaceutical and biotech companies.

SCSB Lunch Series: Social exposure to sickness enhances resilience to infection
2024-04-05 12:00 - 13:00 UTC | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, April 5, 2024
Time: 12:00pm – 1:00pm
Location: Simons Center Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/98747295231)
Speaker: Tomoe Ishikawa, Ph.D.
Affiliation: Simons Postdoctoral Fellow, Choi Lab, Picower Institute, Department of Brain and Cognitive Sciences, MIT
Talk title: Social exposure to sickness enhances resilience to infection
Abstract: Animals change their social engagement based on the health status of their conspecifics to minimize infectious risk. However, it remains unclear whether animals also adjust their own immune status by detecting sick individuals. We have found that prior exposure to sick cagemates alleviates symptoms induced by viral and bacterial infections. This indicates that animals have a proactive immune response upon detecting sickness in their conspecifics. Furthermore, we demonstrated that exposure to sick animals activates an amygdala nucleus, and chemogenetic activation of this amygdala nucleus is sufficient to mitigate signs induced by viral and bacterial infections. These findings suggest that neuroimmune interactions activated by the detection of sick conspecifics modulate the immune system to better cope with subsequent pathogenic infections.

SCSB Colloquium Series: How Nature and Nurture Conspire to Regulate Brain Development and Plasticity [Michael Greenberg, Ph.D.]
2024-03-20 16:00 - 17:00 UTC | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Wednesday, March 20, 2024
Location: 46-3002 (Singleton Auditorium). Please note this event is in person only
Speaker: Michael Greenberg, Ph.D.
Affiliation: Nathan Marsh Pusey Professor of Neurobiology, Harvard Medical School
Host: Dr. Mriganka Sur
Talk title: How Nature and Nurture Conspire to Regulate Brain Development and Plasticity
Abstract: Experience-dependent neuronal activity plays a critical role in shaping the connectivity and function of the central nervous system. These actions are mediated in part by the action of a program of neuronal activity-driven gene expression. Investigation of these gene expression programs has uncovered important roles in dendritic growth, the development of excitatory and inhibitory synapses, the composition of protein complexes at pre- and post-synaptic sites, and the production of neuropeptides that control neural circuit development. Moreover, defects in the activity-dependent gene program contribute to disorders of human cognition. Thus, study of this transcriptional response promises new insights into neuronal plasticity and disease.

SCSB Lunch Series: Quantifying correlations between linguistic surprisal, prosody, and backchannels in naturalistic conversation
2024-03-15 12:00 - 13:00 UTC | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, March 15, 2024
Time: 12:00pm – 1:00pm
Location: Simons Center Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/98903444024)
Speaker: Thomas Clark
Affiliation: PhD student, TedLab and Computational Psycholinguistics Lab, Department of Brain and Cognitive Sciences, MIT
Talk title: Quantifying correlations between linguistic surprisal, prosody, and backchannels in naturalistic conversation
Abstract: Research indicates that more predictable (i.e. less surprising) words are generally reduced in duration. The relationship between surprisal and other prosodic features, as well as listener backchannels (short interjections such as “yeah” or “mhm” that are common in conversation) remains understudied. Using large language models to compute word surprisal, we investigate a new large corpus of naturalistic conversations (CANDOR). We find that surprisal robustly predicts duration, pitch, and intensity even when controlling for possible confounds, and is negatively correlated with backchannels. These preliminary results indicate a sensitivity of both speaker and listener behavior to the information content of words in everyday conversation.

SCSB Colloquium Series: The Intact Mind and Why It Matters [Amy Lutz, Ph.D.]
2024-03-06 16:00 - 17:00 UTC | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Wednesday, March 6, 2024
Location: 46-3002 (Singleton Auditorium) + Zoom Webinar: https://mit.zoom.us/j/91052434159
Speaker: Amy S.F. Lutz, Ph.D.
Affiliation: Senior Lecturer, History and Sociology of Science Department, University of Pennsylvania; Vice-President, National Council on Severe Autism
Host: Dr. Mriganka Sur
Talk title: The Intact Mind and Why It Matters
Abstract: In her 2006 memoir Strange Son, Cure Autism Now co-founder Portia Iversen described the “intact mind” she believed was buried within even the most cognitively impaired autistic individuals, like her son Dov. But the sentiment itself was not new. Emerging largely out of psychoanalytic theory dating back to the mid 20th century, the intact mind was amplified in parent memoirs even as biomedical discourse consolidated in the 1970s around a very different depiction of autism: as a biologically based, intractable neurodevelopmental disorder. With as many as 1 out of every 36 American children now affected, according to the CDC, discourse originally unique to autism has come to inform current debates at the heart of intellectual and developmental disability practice and policy in the United States – including ongoing battles over 14(c) subminimum wage programs, guardianship, and facilitated communication.

SCSB Lunch Series: Human Paraneoplastic antigen Ma2 (PNMA2) forms icosahedral capsids that can be engineered for mRNA delivery
2024-02-23 12:00 - 13:00 UTC | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, February 23, 2024
Time: 12:00pm – 1:00pm
Location: Simons Center Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/93707327771)
Speaker: Yugang Zhang, Ph.D.
Affiliation: Simons Fellow, Feng Zhang Laboratory, McGovern Institute for Brain Research, MIT
Talk title: Human Paraneoplastic antigen Ma2 (PNMA2) forms icosahedral capsids that can be engineered for mRNA delivery
Abstract: To build a protein-based delivery vehicle, we systematically investigate human PNMA proteins and find that a number of PNMAs are secreted by human cells and form capsid in vitro. We determine that PNMA2 forms icosahedral capsids efficiently but does not naturally encapsidate nucleic acids. We resolve the cryo-electron microscopy (cryo-EM) structure of PNMA2 and leverage the structure to design engineered PNMA2 (ePNMA2) particles with RNA packaging abilities. Recombinantly purified ePNMA2 proteins package mRNA molecules into icosahedral capsids and can function as delivery vehicles in mammalian cell lines, demonstrating the potential for engineered endogenous capsids as a nucleic acid therapy delivery modality.

SCSB Colloquium Series: Frequency Modules of Social Reward in the Brain
2024-02-07 16:00 - 17:00 UTC | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Wednesday, February 7, 2024
Location: 46-3002 (Singleton Auditorium) + Zoom Webinar (https://mit.zoom.us/j/97035996656)
Speaker: Steve Chang, Ph.D.
Affiliation: Associate Professor of Psychology and of Neuroscience, Department of Psychology, Department of Neuroscience, Wu Tsai Institute, Kavli Institute for Neuroscience, Yale University
Host: Dr. Mehrdad Jazayeri
Talk title: Frequency Modules of Social Reward in the Brain
Abstract: Social interaction is essential to our daily lives, shaping interpersonal communication and the decisions we make. The first part of the presentation will describe our recent findings from studying the medial prefrontal-amygdala circuits when macaques make prosocial and antisocial decisions impacting the reward outcome of a partner. We found directionally selective ‘frequency modules’ that convey social decision variables (e.g., prosocial versus antisocial preference, vicarious versus experienced reward). These results support the importance of network-level modules in the social brain that are governed by frequency and direction selective information transfer. The second part of the presentation will describe a novel automated cooperation paradigm in freely moving marmosets that combines markerless behavioral tracking and a dynamic Bayesian network modeling of behavioral dependencies. Cooperation in this paradigm was guided by the strategic use of social information and was critically dependent on social relationships. Overall, this presentation emphasizes the importance of interareal interactions in the social brain and introduces a robust naturalistic cooperation paradigm suitable for neural investigation.

SCSB Lunch Series: Probing the cortical circuits that prevent sensory overload
2023-12-15 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 15, 2023
Time: 12:00pm – 1:00pm
Location: Simons Center Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/96426558759)
Speaker: Alex Major, Ph.D.
Affiliation: Past Simons Fellow, Earl Miller Laboratory, Picower Institute for Learning and Memory, MIT
Talk title: Probing the cortical circuits that prevent sensory overload
Abstract: Sensory overload in autism spectrum disorder (ASD) may result from disrupted filtering of predicted sensory inputs. Our Predictive Coding model of brain function suggests sensory information is carried by gamma rhythms in the upper layers of the cortex. In contrast, alpha/beta rhythms are in deep layers and may suppress gamma rhythms of predicted sensory input. We hypothesize feedback prediction signals in ASD are deficient, manifesting as reduced alpha/beta rhythms. This causes less suppression of incoming sensory input and gamma, leading to sensory overload. We have developed a technique to simulate sensory overload in rhesus monkeys by suppressing deep layers of prefrontal cortex. This is hypothesized to decrease feedback alpha/beta activity and thus disinhibit gamma activity and sensory input. This will directly test a mechanism of sensory overload, perhaps leading research towards improved symptom management.

SCSB Colloquium Series: The neurobiology of social isolation
2023-12-06 16:00 - 17:00 UTC | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Wednesday, December 6, 2023
Location: 46-3002 (Singleton Auditorium) and YouTube Stream (https://youtube.com/live/89g148lSIco)
Speaker: Moriel Zelikowsky, Ph.D.
Affiliation: Assistant Professor, Department of Neurobiology, University of Utah
Host: Dr. Steve Flavell
Talk title: The neurobiology of social isolation
Abstract: We are social animals. Extended deprivation of social contact can produce deleterious effects on the brain and behavior. Our group works to identify the neural circuit mechanisms which give rise to the internal brain state produced by prolonged social isolation and its impact on survival-related social behaviors. I will present some of our recent work examining the effects of social isolation on mouse courtship behavior and vocal communication using in-depth behavioral and acoustic analyses, machine vision, genetically-targeted cellular perturbations, and in vivo imaging in mice. Collectively, our findings reveal a dramatic disruption of mouse courtship behavior and social communication after isolation, and identify a unique neural signature in the coding of this brain state.

SCSB Lunch Series: A network of brain areas is sensitive to prosody and distinct from language and auditory areas
2023-11-17 12:00 - 13:00 (America/New_York) | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, November 17, 2023
Time: 12:00pm – 1:00pm
Location: Singleton Auditorium 46-3002 + Zoom Meeting (https://mit.zoom.us/j/93332201270)
Speaker: Tamar Regev, Ph.D.
Affiliation: Postdoctoral Associate, Ev Fedorenko Laboratory, MIT; Fellow of the Poitras Center for Psychiatric Research
Talk title: A network of brain areas is sensitive to prosody and distinct from language and auditory areas
Abstract: Prosody refers to auditory features of speech beyond phonetics, like pitch and tempo, which convey linguistic, emotional, and other socially-relevant information. Does the brain contain specialized areas for processing prosody or is prosodic information processed by known auditory or language areas? Using fMRI, we identified temporal and frontal brain areas which were strongly sensitive to prosody with or without linguistic content. These prosody-sensitive areas were adjacent to but distinct from language areas which extract meaning from linguistic input, and from auditory areas that support pitch perception and speech perception. Interestingly, these areas showed some response to communicative signals, especially facial expressions and non-speech vocalizations. These results suggest that prosody is processed by a network of brain areas that lie in close proximity to language-selective areas and are broadly sensitive to non-linguistic communicative cues. This work lays a critical foundation for further investigations of the neural basis of prosodic processing and its disorders.
Bio: Dr. Tamar Regev is a Postdoctoral Associate at BCS, MIT, working with Prof. Ev Fedorenko, and is a fellow of the Poitras Center for Psychiatric Research. She earned her Ph.D. in Computational Neuroscience from The Hebrew University of Jerusalem, where she was advised by Prof. Leon Y. Deouell and Prof. Israel (Eli) Nelken, and conducted research on representations of auditory frequency using EEG and computational modeling. She holds a M.Sc in Cognitive Systems from UPF, Barcelona, and a B.Sc in Physics and Biology from Tel-Aviv University.

SCSB Colloquium Series: Modeling brain overgrowth in autism using human pluripotent stem cells
2023-11-08 16:00 - 17:00 (America/New_York) | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Wednesday, November 8, 2023
Location: 46-3002 (Singleton Auditorium) and YouTube Stream (https://youtube.com/live/4vzPAvJGbfo)
Speaker: Sundari Chetty, Ph.D.
Affiliation: Assistant Professor, Center for Regenerative Medicine, MGH; Department of Psychiatry, Harvard Medical School; Principle Faculty Member, Harvard Stem Cell Institute
Host: Dr. Dara Manoach
Talk title: Modeling brain overgrowth in autism using human pluripotent stem cells
Bio & Abstract: Dr. Sundari Chetty is an assistant professor at the Center for Regenerative Medicine at Massachusetts General Hospital (MGH) and the department of Psychiatry at Harvard Medical School. She also serves as a Principal Faculty member of the Harvard Stem Cell Institute. Dr. Chetty received her PhD in neuroscience and B.A. in molecular and cellular biology from the University of California, Berkeley. Dr. Chetty started her lab at Stanford University after completing her postdoctoral work in Stem Cell and Regenerative Biology at Harvard University in Douglas Melton’s laboratory. In June of 2022, she relocated her laboratory to MGH.
The overarching goal of Dr. Chetty’s lab is to understand the mechanisms underlying neurodevelopmental and psychiatric disorders, such as autism spectrum disorder and schizophrenia, and identify novel therapeutic targets based on these mechanistic insights. In particular, her lab has been investigating the mechanisms underlying brain overgrowth or undergrowth in these disorders using human induced pluripotent stem cell (iPSC) technology. Using human iPSCs from idiopathic patients as well as those with known genetic variations, the Chetty lab uses two-dimensional and brain organoid models to investigate changes at the cellular, functional, and mechanistic levels using a broad range of techniques from RNA sequencing, genome editing, to functional assays in in vitro and in vivo models. This talk will highlight recent work in the Chetty lab investigating how interactions between the neuroimmune system regulate brain overgrowth in autism and other neurodevelopmental disorders.

SCSB Colloquium Series: Individual variation in neuroanatomy within autism
2023-10-25 16:00 - 17:00 (America/New_York) | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Portrait of Assistant Professor Stefano Anzellotti (Psychology) photographed in a classroom and outside of McGuinn for Kalscheur SJ web slide show and a future issue of Welcome Additions in Chronicle.
Date: Wednesday, October 25, 2023
Location: 46-3002 (Singleton Auditorium) and YouTube Stream (https://youtube.com/live/lF-TI7anPZs)
Speaker: Stefano Anzellotti, Ph.D.
Affiliation: Assistant Professor, Boston College
Host: Dr. Rebecca Saxe
Talk title: Individual variation in neuroanatomy within autism
Abstract: Autism spectrum disorder is very heterogeneous. Diagnosed individuals vary in terms of genetics, neural measures, and behavior. Heterogeneity has two important implications for autism research. First, it makes it more difficult to identify findings that replicate, hindering the progress of research. Second, different individuals are likely to need different, personalized interventions. Therefore, understanding individual variation within autism is a key research objective. A major obstacle to this objective is the fact that individual variation related to autism is mixed with unrelated variation, which also occurs in the general population. We find that a recently developed deep learning method — Contrastive Variational Autoencoders — makes it possible to disentangle autism-related individual variation in brain anatomy from variation that is shared with the general population. In turn, this process reveals previously hidden relationships between individual differences in brain anatomy and individual differences in behavioral symptoms. Finally, we use counterfactual AI to identify interpretable anatomical sites of individual variation within autism, associating differences in behavioral symptoms with changes at specific anatomical loci. This approach can also be applied to other data modalities and other disorders, offering a technique to study individual variation specific to a particular population of participants.

SCSB Lunch Series: Probing Cholinergic Brain Function Using Multimodal Molecular Imaging
2023-10-20 12:00 - 13:00 UTC | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, October 20, 2023
Time: 12:00pm – 1:00pm
Location: SCSB Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/91735453120)
Speaker: Sajal Sen, Ph.D.
Affiliation: Simons Postdoctoral Fellow, Alan Jasanoff Laboratory, MIT
Talk title: Probing Cholinergic Brain Function Using Multimodal Molecular Imaging
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: Synapses and Me
2023-10-04 16:00 - 17:00 UTC | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Wednesday, October 4, 2023
Location: 46-3002 (Singleton Auditorium) and YouTube Stream (https://youtube.com/live/lCJGajRrG34)

Speaker: Gerald Fischbach, MD
Affiliation: Distinguished Scientist and Fellow, Simons Foundation
Host: Dr. Mriganka Sur

Talk title: Synapses and Me
Abstract: Throughout my 60 years in biomedical science, I have been focused on chemical synapses in the brain and peripheral nervous system. I began by studying the vertebrate neuromuscular junction. Electrophysiology led to biochemical and genetic analyses focused on how “trophic” factors released from motor nerve terminals regulate the number and distribution of acetylcholine receptors in the postsynaptic muscle membrane. As my lab grew and as I took on more administrative responsibilities, including Chairmanships at Washington University and at Harvard Medical School, Directorship of NINDS and finally Chief Scientist at the Simons Foundation Autism Research Initiative my interests broadened. My research moved up the neural axis from the spinal cord to the midbrain and the cerebral cortex, and my interests grew as well. Molecular, biology systems science and computational approaches are opening new ways of thinking about synapses and behavior. It is simply not enough to say that autism is a “synaptopathy”.
Bio:
Gerald Fischbach joined the Simons Foundation in 2006 to oversee the Simons Foundation Autism Research Initiative (SFARI). He then became the foundation’s first chief scientist and fellow and currently holds the title of Distinguished Scientist and Fellow. He is formerly the dean of the Faculties of Health Sciences at Columbia University, and director of the National Institute of Neurological Disorders and Stroke at the National Institutes of Health from 1998-2001, Fischbach received his M.D. degree in 1965 from Cornell University Medical School and interned at the University of Washington Hospital in Seattle. He began his research career at the National Institutes of Health, serving from 1966-1973. He subsequently served on the faculty of Harvard Medical School, first as associate professor of pharmacology from 1973-1978 and then as professor until 1981. From 1981-1990, Fischbach was the Edison professor of neurobiology and head of the Department of Anatomy and Neurobiology at Washington University School of Medicine. In 1990, he returned to Harvard Medical School where he was the Nathan Marsh Pusey professor of neurobiology and chairman of the neurobiology departments of Harvard Medical School and Massachusetts General Hospital until 1998.
Throughout his career, Fischbach has studied the formation and maintenance of synapses, the contacts between nerve cells and their targets through which information is transferred in the nervous system. He pioneered the use of nerve cell cultures to study the electrophysiology, morphology and biochemistry of developing nerve-muscle and inter-neuronal synapses. His current research is focused on roles that neurotrophic factors play in determination of neural precursor fate, synapse formation and neuronal survival.
Fischbach is a past president of the Society of Neuroscience and serves on several medical and scientific advisory boards. He is a member of the National Academy of Sciences, the American Academy of Arts and Sciences and the Institute of Medicine. He is a fellow of the American Association for the Advancement of Science and a former non-resident fellow of the Salk Institute.

SCSB Lunch Series: Advanced Genetic Therapies for the Treatment of Rett Syndrome
2023-09-29 12:00 - 13:00 UTC | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
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 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

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?
