Simons Center for the Social Brain

SCSB Lunch Series: Joshua Tenenbaum, Ph.D.
2017-05-19 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, May 19, 2017
Time: 12:00pm – 1:00pm
Speaker: Joshua Tenenbaum, Ph.D.
Affiliation: Professor of Computational Cognitive Science, Department of Brain and Cognitive Sciences, MIT
Talk Title: Computational Models of Social Cognition
Abstract: to be provided later…

SCSB Lunch Series: Ev Fedorenko, Ph.D.
2017-07-07 12:00 - 13:00 | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, July 7, 2017
Time: 12:00pm – 1:00pm

Speaker: Ev Fedorenko, Ph.D., Assistant Professor, Department of Psychiatry, HMS; Associate Researcher, MGH; Research Affiliate, Department of Brain and Cognitive Sciences, MIT
Talk title: A search for candidate brain-based biomarkers of autism
Abstract: I will talk about two lines of work aimed at discovering brain-based biomarkers of autism.
1. One of the few replicated functional brain differences between individuals with autism spectrum disorders (ASD) and neurotypical (NT) controls appears to be reduced lateralization of language (e.g., Lindell & Hudry, 2013). However, most prior reports have examined differences between ASD and NT individuals at the group level, making interpretation difficult. Using a validated fMRI measure of language lateralization, which is robust at the individual-subject level (Mahowald & Fedorenko, 2016), we compared the degree of lateralization between 28 ASD participants and pairwise-matched NT participants. ASD participants showed less lateralized language responses (due to more robust right hemisphere activations). We then asked whether reduced language lateralization is an endophenotype of disrupted neural development that is associated with autism-related features in NT participants. Indeed, we found that autistic trait load was associated with more bilateral language activations in a set of 139 NT participants. Furthermore, NT male participants (n=42) showed more bilateral language activations than matched (including for autistic trait load) NT female participants, in line with a higher incidence of autism in males. In tandem, these results suggest that reduced lateralization of the language system is a robust neural marker of autism, present in both NT males and NT individuals with high autistic trait load, in line with the complexity of the genetic basis of autism with numerous genes implicated, and each gene explaining only a small proportion of variance.
2. When we understand language, we flexibly use our knowledge of the speaker’s mental states (e.g., Brennan et al., 2010). Do we also keep track of what other listeners do or do not understand? In an ERP study, Rueschmeyer et al. (2015) observed that when a listener knows that a co-listener cannot understand the utterance (e.g., “The girl had a beak and yellow feathers”) because they are lacking the relevant context (e.g., “The girl dressed up as a canary for Halloween”), they show a marker of comprehension difficulty: an N400 effect (Kutas & Hillyard, 1980) to a word (“beak” in the example above) that makes sense to the listener, but not to the co-listener. We term this effect the Social or Empathetic N400. Across two ERP experiments with NT participants, we (i) replicate the Social N400 effect, (ii) show that it obtains spontaneously in the presence of a (confused) co-listener (cf. explicit instructions to think about the co-listener’s mental state in Rueschmeyer’s study), and (iii) show that the magnitude of this effect is related to social abilities. In an ongoing study with ASD participants, we are testing whether the social N400 effect may be reduced or absent.

SCSB Lunch Series: Ian Wickersham, Ph.D.
2017-08-25 12:00 - 13:00 | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, August 25, 2017
Time: 12:00pm – 1:00pm
Speaker: Ian Wickersham, Ph.D.
Affiliation: Principal Research Scientist, McGovern Institute for Brain Research, MIT
Talk Title: Cell-type-specific transgene expression in wild-type animals using endogenous proteins as skeletons for assembling split transcription factors
Abstract: Cell-type-specific manipulations, such as optogenetic or chemogenetic stimulation and inhibition, are critical for dissecting circuit function and dysfunction, but their use so far has almost entirely been restricted to genetically tractable species, in which genomic engineering – such as the insertion of the Cre gene into the parvalbumin locus – is used to restrict transgene expression to a functionally meaningful cell type of interest. Here we introduce a technology for causing expression of transgenes specifically within targeted cell types in wild-type animals. Engineered binding proteins specific to a targeted endogenous protein are separately fused to the two fragments of a split transcription factor. In the presence of the targeted protein, the fusion proteins bind to single molecules of the targeted protein, reconstituting a functional transcription factor complex which causes transgene expression from an exogenously introduced template.
Here we show that this approach can be used to achieve high expression of transgenes selectively in cells expressing calretinin, a calcium binding protein characteristic of important interneuronal subtypes in cerebral cortex, hippocampus, and other brain structures. Using the directed evolution technique of yeast surface display, we engineered binding proteins specific to calretinin, then constructed genetic fusions of the two binding proteins to various DNA binding domains and transcriptional activation domains. We show that the system is robust and modular, working with a variety of DNA binding domains and activation domains in various configurations. We show that the system can be delivered via adeno-associated viral vectors injected stereotaxically in order to cause targeted expression of EGFP or channelrhodopsin specifically in calretinin-expressing neurons in neocortex and hippocampus of wild-type mice and rats. Using whole-cell recordings in acute brain slices, we show that targeted fluorophore expression can be used to selectively record from the neuronal type of interest and that channelrhodopsin is expressed highly enough to allow optical control of the neurons’ activity.
This represents the first successful cell-type-specific transgene expression within any cortical interneuron subtype in wild-type animals of any species.

SCSB Lunch Series: Hector Luis Penagos-Vargas, Ph.D.
2017-09-22 12:00 - 13:00 | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, September 22, 2017
Time: 12:00pm – 1:00pm
Speaker: Hector Luis Penagos-Vargas, Ph.D.
Affiliation: Research Scientist, Wilson Laboratory, Picower Institute for Learning and Memory, MIT
Talk Title: Increases in reward elicit the expression of a joint offline state in the rodent hippocampus and retrosplenial cortex.
Abstract: The hippocampus is a brain structure implicated in a range of cognitive functions including navigation, planning, imagination and the formation of episodic memories. The reactivation, or replay, of hippocampal spiking patterns during sleep and periods of quiet waking has been associated with memory consolidation or navigation and planning, respectively. All these functions rely on the successful integration of information by the neocortex, which may be mediated by hippocampal replay. Consistent with this notion, different regions of neocortex have been shown to engage in a bidirectional dialog with the hippocampus during periods of sleep reactivation. Contrasting with this well-established sleep interaction, little is known about how the hippocampus and neocortex interact during awake replay. In this talk, I will describe a novel waking state in which the hippocampus and retrosplenial cortex, a structure also implicated in higher cognitive functions, jointly transition into an offline state in which they replicate well-known sleep relationships. Understanding these interactions at a mechanistic level could yield insights into cortical integration, which tends to be affected in neurological disorders.

SCSB Lunch Series: Nader Morshed
2017-10-20 12:00 - 13:00 | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, October 20, 2017
Time: 12:00pm – 1:00pm
Speaker: Nader Morshed
Affiliation: Graduate Student, White Lab, David H. Koch Institute for Integrative Cancer Research, MIT
Talk Title: Using phosphoproteomics to study signaling dysregulation in neurodevelopmental and neurodegenerative diseases.
Abstract: Cellular signaling networks play an essential role in brain function and are commonly mediated by protein phosphorylation. Using mass spectrometry, we have quantified protein phosphorylation changes in models of Rett’s syndrome and Alzheimer’s disease. This phosphoproteome allows us to link cellular phenotypes, such as synaptic deficits or glial responses, to the dysregulation of the kinases and phosphatases coordinating them. We hope that by understanding which signaling pathways are disrupted in brain development and aging, we may be able to identify new treatments for patients.

SCSB Lunch Series: David C. Page, Ph.D.
2017-10-27 12:00 - 13:00 | Singleton Auditorium, Bldg. 46, Room 3002, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, October 27, 2017
Time: 12:00pm – 1:00pm
Speaker: David C. Page, Ph.D.
Affiliation: Director, Whitehead Institute; Professor of Biology, MIT; Investigator of the Howard Hughes Medical Institute
Talk Title: “Sex and Disease: Do males and females read their genomes differently?”
Abstract:
“Nothing in biology makes sense except in the light of evolution.”
Theodosius Dobzhansky, 1973
Dobzhansky’s oft-quoted dictum is highly relevant to our understanding of the manifold differences between males and females in health and disease, both within and beyond the reproductive tract. From the origins of sexual reproduction, in single-celled organisms, to the morphing of our own sex chromosomes from ordinary autosomes during the past 200-300 million years, comparative and evolutionary analyses offer deep, biologically grounded insights into the epigenetic, genomic, and phenotypic differences between the sexes. The emerging evolutionary view serves as an alternative, or complement, to the model (chromosomal sex → gonadal sex → phenotypic sex) that has guided teaching and research for the last half century. The opportunity now presents itself to capitalize upon this emerging evolutionary view of sex differences and their origins.
Most recently, my colleagues and I have conducted comparative genomic and evolutionary studies of the sex chromosomes of humans, other mammals, birds, and reptiles. These studies have revealed that the Y chromosome’s gene content became specialized, through natural selection, to maintain the ancestral dosage of homologous X-Y gene pairs that function as broadly expressed regulators of the genome and gene activity; these X-Y gene pairs regulate transcription, translation and protein stability (Bellott et al. [2014] Nature 508: 494; Bellott et al. [2017] Nature Genetics 49: 387). As a result, there exists a fundamental sexual dimorphism, at a biochemical level, and throughout the body, that derives directly from genetic differences between the X and Y chromosomes. This fundamental sexual dimorphism may play an unappreciated role in health and disease in both males and females.
***Please note this event will be held in Singleton Auditorium (46-3002)

SCSB Lunch Series: Ritchie Chen, Ph.D.
2017-11-03 12:00 - 13:00 | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, November 3, 2017
Time: 12:00pm – 1:00pm
Speaker: Ritchie Chen, Ph.D.
Affiliation: Postdoctoral Fellow, Chung Laboratory, Institute for Medical Engineering and Science, MIT
Talk Title: Simultaneous profiling of nucleotides, proteins, and fluorescence activity in transparent tissue enabled by flexible and multifunctional fixatives.
Abstract: Holistic understanding of complex biological systems, from single biomolecules to cell interactions across whole organs, will require integrated methodologies that can simultaneously probe both nucleotides and proteins in intact tissue. While several fixation strategies have been explored to preserve individual molecular features (e.g fluorescent activity of protein reporters, mRNA transcripts, or protein antigenicity), a universal tissue clearing method to profile all biomolecule types remains to be developed. Here, we demonstrate how multifunctional cross-linkers with tightly regulated reaction kinetics can form cohesive tissue gels by binding together biomolecules of interest. We find that these flexible and multifunctional linkers protected proteins and nucleotides from deteriorating in harsh chemical conditions by forming both intra- and intermolecular bonds. This strategy, called SHIELD, enables simultaneous molecular profiling of nucleotides, proteins, and fluorescent reporters in intact tissue, such that correlative studies, from single transcripts to whole organ features, can be performed.

SCSB Lunch Series: Mehmet Kanik, Ph.D.
2017-12-01 12:00 - 13:00 | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, December 1, 2017
Time: 12:00pm – 1:00pm
Speaker: Mehmet Kanik, Ph.D.
Affiliation: Simons Postdoctoral Fellow, Polina Anikeeva Lab, Research Laboratory of Electronics, Department of Materials Science and Engineering, MIT
Talk Title: Brain Challenges and Materials Solutions.
Abstract: Electrophysiological recording requires precise tools that produce minimal tissue damage while allowing stable and reliable, low signal to noise ratio recording from specific regions of the brain. Probes made of stiff materials that have a significant mechanical mismatch with the brain cause drastic changes in neural dynamics in both chronic and acute implantations. Probes fabricated using metals, glasses, and semiconductors often fail to deliver high-quality recording in long-term experiments. Next generation neural probes should be designed to integrate multiple capabilities such as simultaneous light delivery and electrophysiological recording, infusion of pharmacological compounds and viral vectors, while maintaining a small footprint (< 500 um) to accommodate repeated behavioral evaluation over the course of several months.
Recently developed fiber-based flexible devices use biocompatible materials which exhibit mechanical properties similar to the brain. In addition, polymer probes developed in the Bioelectronics lab address the challenges in neural probe engineering by enabling simultaneous electrical recording, optical excitation, and microfluidic functions while reducing the foreign body response as compared to commercially available tools. Here, we introduce fiber neural probes to map the cortical circuits involved in interleukin-17a (IL-17a) dependent maternal immune activation (MIA) driven autism spectrum disorder (ASD) mouse model.

SCSB Lunch Series: Michael Strano, Ph.D.
2017-12-08 12:00 - 13:00 | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, December 8, 2017
Time: 12:00pm – 1:00pm
Speaker: Michael Strano, Ph.D.
Affiliation: Carbon P. Dubbs Professor, Department of Chemical Engineering, MIT
Talk Title: Applications of Nanosensors to Understanding Biochemical Signaling Within the Human Body
Abstract: The human body is a vast network of biochemical signaling pathways dictating physiological and pathological processes. To probe this network, our research group has introduced Corona Phase Molecular Recognition, or CoPhMoRe, for discovering synthetic, heteropolymer corona phases that form molecular recognition sites at the nanoparticle interface. By screening libraries of synthetic heteropolymers chemically adsorbed onto single-walled carbon nanotubes (SWNT), we have engineered new optical biosensors that exhibit highly selective recognition for specific molecules, including riboflavin, L-thyroxine, dopamine, nitric oxide, sugar alcohols, estradiol, as well as proteins such as fibrinogen. The results have significant potential in that nanoparticles such as SWNT can be interfaced to biological systems at the sub-cellular level, allowing monitoring of sub-cellular, cellular, tissue, and whole-organism processes. With deep tissue penetration, we demonstrated our nanosensors in vitro with no photobleaching, and in vivo with no fluorescence degradation (400+ days).
Engineering the nanoparticle corona in this way offers significant potential to translate sensor technology to previously inaccessible environments. We have measured dopamine efflux from PC12 cells, which may allow monitoring of neuroendocrine production and signaling. Additionally, we have synthesized selective cortisol and progesterone sensors and are currently performing in vivo measurements of progesterone in mice. Cortisol has been implicated in numerous pathological conditions, including depression, post-traumatic stress disorder, bipolar disorder, and autism, whereas progesterone is the primary female sex hormone dictating fertility. Monitoring these, as well as other steroid hormones, could provide significant insight about the etiology of various endocrine-related pathologies. In the diabetes space, we have synthesized an insulin sensor and are currently designing glucose responsive insulins (GRI). Interfacing insulin sensors and a GRI with currently available continuous glucose monitors may revolutionize diabetes treatment, as insulin dosages will be more tightly controlled in a closed loop fashion. Last, I will discuss our current work in cancer. One major challenge in cancer is the ability to have an accurate and comprehensive picture of the intratumoral delivery and localization of chemotherapeutic drugs. The tumor heterogeneity has a significant impact on drug delivery, drug uptake, and therapeutic effectiveness. Our nanosensor platform can provide real-time spatiotemporal information about tumor metabolites and chemotherapeutic drug delivery. This feedback will give physicians and patients information about the tumor molecular response significantly earlier in a matter of hours or days compared to the weeks or months needed to see measurable size changes on CT or MRI.

SCSB Lunch Series: Ted Gibson, Ph.D.
2018-02-09 12:00 - 13:00 | MA
Date: Friday, February 9, 2018
Time: 12:00pm – 1:00pm
Speaker: Ted Gibson, Ph.D.
Affiliation: Professor of Cognitive Science, Department of Brain & Cognitive Sciences, MIT
Talk Title: The structure of pragmatic reasoning and the scope of the communicative impairment in ASD.
Abstract: Language comprehension entails more than simply decoding the literal meaning of an utterance: our interpretation is powerfully shaped by the perceived intent of the speaker, the linguistic and social context of the utterance, and our general world knowledge. This ability to exploit speaker intent and background knowledge to go beyond the literal meaning is referred to as “pragmatics”, and is at the core of communicative success. The term “pragmatics”, as used in the literature, encompasses a wide range of diverse phenomena, from irony and sarcasm, to understanding scalar implicatures, to using prosodic cues, to making world-knowledge-based inferences. In an ongoing project, we are using an individual-differences approach to investigate the structure of mental processes relevant to pragmatic reasoning. To do this, we developed an extensive battery consisting of 20 tasks that tap 11 distinct phenomena. Across a large sample of neurotypical adults (n=~400) tested on Mechanical Turk, factoring out IQ, we discovered a remarkably clear clustering of tasks into sensible categories. The biggest category included phenomena that appear to involve higher-order expectations about social norms, like irony, white lies, and humor. Other categories included world-knowledge-based inferences, prosodic processing, and understanding scalar implicatures. We then asked which of these components of pragmatic reasoning are impaired in individuals with ASD. In a sample of 18 participants (data collection ongoing), we found impairments in a) the component that deals with higher-order expectations about social norms, and b) world-knowledge-based inferences, but not in prosodic processing or understanding scalar implicatures. Thus, we are making some progress in both carving up the mental architecture of pragmatic processing, and trying to delineate the scope of the communicative impairment in ASD.

SCSB Lunch Series: Dara Manoach, Ph.D.
2018-02-16 12:00 - 13:00 | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, February 16, 2018
Time: 12:00pm – 1:00pm
Speaker: Dara S. Manoach, Ph.D.
Affiliation: Professor of Psychology, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School
Talk Title: Abnormal sleep spindles in neurodevelopmental disorders: Treatable endophenotypes that link risk genes to impaired cognition?
Abstract: Although neurodevelopmental disorders are defined by waking phenomena, abnormal sleep is a pervasive feature that may contribute to their manifestations. In schizophrenia, there is convincing evidence that sleep spindle deficits impair memory consolidation. Sleep spindles, a defining EEG oscillation of Stage 2 sleep, are initiated in the thalamic reticular nucleus and are a product of thalamocortical interactions. I will review evidence that spindle deficits in schizophrenia are: (i) genetically-mediated, (ii) associated with abnormal thalamocortical interactions, (iii) impair sleep-dependent memory consolidation, (iv) contribute to symptoms and (v) are a novel treatment biomarker. I will end by describing our collaborative study of sleep spindles in autism.
Dara Manoach is a Professor of Psychology in the Department of Psychiatry at Massachusetts General Hospital and Harvard Medical School. She is a neuropsychologist whose research program uses multimodal neuroimaging to illuminate the neural bases of cognitive deficits in neuropsychiatric and neurodevelopmental disorders, particularly schizophrenia and autism. The ultimate goal of this work is to identify mechanisms of cognitive impairment that can guide the development of treatment. Her primary area of research focuses on the contribution of abnormal sleep to memory consolidation deficits. Dr. Manoach received her doctorate from Harvard University in Experimental Psychology, completed a clinical psychology internship at McLean Hospital and a postdoctoral fellowship in clinical neuropsychology at Beth Israel Hospital of Harvard Medical School. At MGH she directs the Laboratory for Multimodal Neuroimaging of Cognition in Psychopathology (Manoach Lab) at the Athinoula A. Martinos Center for Biomedical Imaging.

SCSB Lunch Series: Siyuan Rao, Ph.D.
2018-03-23 12:00 - 13:00 | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, March 23, 2018
Time: 12:00pm – 1:00pm
Speaker: Siyuan Rao, Ph.D.
Affiliation: Polina Anikeeva Laboratory, Research Laboratory of Electronics and Simons Center for Social Brain, MIT
Talk Title: Magnetochemogenetic Technique for Remote Manipulation of Genetically Identifiable Neurons
Abstract: For the rodent models of Autism Spectrum Disorders, whose behavior is sensitive to the implanted foreign objects, investigation of the neural circuits underlying their abnormal behavioral phenotypes via invasive optogenetic and electrical neuromodulation devices poses a challenge. Here we developed a minimally invasive neuromodulation tool for magnetothermal deep brain interrogation of genetically identifiable neural populations in freely moving rodents. This approach enabled temporally and spatially precise chemical manipulation of neural activity by local release of designer drugs in response to remote exposure to alternating magnetic fields. We achieved the implant-free convenience of magnetothermal neuromodulation concomitantly with the genetic precision of chemogenetics, and thus enabled spatial and temporal modulation for behavioral investigation. We anticipate that the magnetochemogenetic tools will facilitate investigation of neural circuits during behavioral experiments and enable neuromodulation studies in rodent models incompatible with permanently implanted hardware.

SCSB Lunch Series: Caroline Robertson, Ph.D.
2018-04-06 12:00 - 13:00 | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, April 6, 2018
Time: 12:00pm – 1:00pm
Speaker: Caroline Robertson, Ph.D.
Affiliation: Postdoctoral Fellow, MIT McGovern Institute, Incoming Assistant Professor, Dartmouth College
Talk Title: “Advancing a Marker of Reduced GABAergic Action in the Autistic Brain: Pharmacological Investigations”
Abstract: We have recently developed a robust and replicated behavioral marker of autism in visual perception — reduced perceptual suppression during binocular rivalry (Robertson et al., 2013, JNeuro) — which links to the reduced action of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the autistic brain (Robertson et al., 2016, Current Biology).
Our current work aims to develop this marker as tool to facilitate animal and genetic research and pharmacological interventions in the condition. Towards this end, here we tested a causal link between the strength of perceptual suppression during rivalry and the inhibitory neurotransmitter, GABA, using pharmacological manipulations.
22 healthy adults participated in each of three separate studies, investigating the effects of a GABAA modulator (Clobazam; study 1), a GABAB modulator (Arbaclofen; study 2), and a Cl- channel modulator (Bumex; study 3) on binocular rivalry dynamics. Each study took place over 3 days, in a counter-balanced double-blind design. On each of the experimental days, a participant was given either a drug or a placebo, and participated in a short binocular rivalry experiment after the drug had come into effect. Each GABAergic modulator exerted a strong effect and specific effect on perceptual suppression during rivalry. Importantly, binocular rivalry dynamics were highly test-retest reliable across testing days (all Rho > 0.65, all p < 0.001), and measures of drowsiness did not influence key results.
These findings provide a causal, mechanistic link between the GABA pathway and perceptual suppression, as suggested by our previous Magnetic Resonance Spectroscopy research and computational models of rivalry. These results also identify specific aspects of the GABAergic pathway which are involved in supporting binocular rivalry. All in all, our results flag perceptual suppression as a marker of GABAergic drug response.

SCSB Lunch Series: Julian Jara-Ettinger, Ph.D.
2018-04-27 12:00 - 13:00 | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, April 27, 2018
Time: 12:00pm – 1:00pm
Location: Simons Center Conference Room, Building 46, Room 6011, 6th Floor, MIT (43 Vassar Street, Cambridge, 02139 MA)
Speaker: Julian Jara-Ettinger, Ph.D.
Affiliation: Assistant Professor of Psychology and Computer Science, Yale University
Talk Title: “Computational principles underlying social cognition: similarities and differences in ASD”
Abstract: Autistic Spectrum Disorders are diagnosed partly on the basis of impairments in social cognition. However, understanding the exact nature of these deficits has been difficult because there is no characterization of the nature of social inferences in typical development. In this talk I will present a theory of social cognition that posits a naïve utility calculus as the engine for making sense of the social world. I will show that even young children rely on this naïve utility calculus when they interpret other people’s actions, when they make moral evaluations, and when they interpret what other people say. Next, I will present a formal computational model that predicts with quantitative accuracy how neurotypical adults reason about simple social events, and I will show how, by using this model, we can uncover fine-grained similarities and differences in autistic adults.

SCSB Lunch Series: Sasha Krol, Ph.D.
2018-05-04 12:00 - 13:00 | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, May 4, 2018
Time: 12:00pm – 1:00pm
Location: Simons Center Conference Room, Building 46, Room 6011, 6th Floor, MIT (43 Vassar Street, Cambridge, 02139 MA)
Speaker: Sasha Krol, Ph.D.
Affiliation: Simons Fellow, Feng Lab, McGovern Institute, MIT
Talk Title: “Uncovering the developmental and circuit origin of ASD-associated aggression”
Abstract: In addition to core symptoms including social deficits and repetitive behaviors, individuals with autism spectrum disorder (ASD) experience many other debilitating symptoms including aggression, an extremely challenging social disruption. Although dysfunction of hypothalamic circuitry has long been appreciated to be a key mediator of aggression in animal studies, increased aggression in the context of ASD is poorly understood due to a lack of good models. To address this gap, we are using a neurodevelopmental/ASD mouse model of human patients with deletion of PTCHD1, a condition that contributes to ~1% of ASD cases with intellectual disability (ID) and leads to hyper-aggression, a behavior which is recapitulated in the Ptchd1 mutant mouse. Using this model we are determining the circuitry responsible for Ptchd1- mediated, ASD-related aggression. Additionally we are dissecting the temporal requirement of Ptchd1 in the development of aggressive behavior. Together our results will identify a target circuit and temporal window for designing and testing therapies for aggression in ASD and other disorders.

SCSB Lunch Series: Jeong-Tae Kwon, Ph.D.
2018-06-01 12:00 - 13:00 | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, June 1, 2018
Time: 12:00pm – 1:00pm
Location: Simons Center Conference Room, Building 46, Room 6011, 6th Floor, MIT (43 Vassar Street, Cambridge, 02139 MA)

Speaker: Jeong-Tae Kwon, Ph.D.
Affiliation: Simons Postdoctoral Fellow, Gloria Choi Laboratory, McGovern Institute for Brain Research, MIT
Talk Title: “Neuromodulatory Control of Social Behavior in Amygdala”
Abstract: Innate social behaviors, such as reproduction and aggression, need to be tightly regulated to prevent inappropriate social interactions under adverse conditions. While previous studies have mostly focused on the induction of innate social behaviors, neural circuits and mechanism, by which these behaviors are inhibited under inappropriate conditions, are poorly understood. I will present our recent finding that the posteromedial cortical amygdala plays a key role in suppression of social behaviors, such as mounting and attacking, in the adverse conditions (e.g. infectious conspecifics or unfamiliar place). Our results suggest that the suppression effect is mediated through thyrotropin-releasing hormone (TRH) signaling in intra-amygdala circuits. Together, these findings will provide a new understanding into how neuromodulatory signaling in the amygdala guides relevant behavioral outputs that are based on the conditions an individual encounters.

SCSB Lunch Series: Laurel Gabard-Durnam, Ph.D.
2018-09-14 12:00 - 13:00 | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, September 14, 2018
Time: 12:00pm – 1:00pm
Location: Simons Center Conference Room, Building 46, Room 6011, 6th Floor, MIT (43 Vassar Street, Cambridge, 02139 MA)
Speaker: Laurel Gabard-Durnam, Ph.D.
Affiliation: Autism Science Foundation Postdoctoral Fellow, Labs of Cognitive Neuroscience, Boston Children’s Hospital, Harvard Medical School
Talk title: “Neuroimaging evidence for Autism biomarkers across the first year of life”
Abstract: An outstanding issue in Autism Spectrum Disorder (ASD) research is the identification of biomarkers to expedite detection and provide insight into pathophysiology. The search for early neuroimaging biomarkers is both promising and challenging as they occur before behavioral symptoms emerge but during extensive changes in brain function. I will present evidence from 2 longitudinal EEG studies in infants at low- and high-familial risk for ASD that leverage neurodevelopmental changes to identify early biomarkers. These studies show that EEG within the first year of life differentiates infants with future ASD diagnoses, and they provide a mechanism through which disrupted neuroplasticity contributes to ASD. Together, these findings speak to the potential of early EEG-based biomarkers for identifying and understanding neurodevelopmental trajectories in ASD.

SCSB Lunch Series: Yang Zhou, Ph.D.
2018-10-05 12:00 - 13:00 | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, October 5, 2018
Time: 12:00pm – 1:00pm
Location: Simons Center Conference Room, Building 46, Room 6011, 6th Floor, MIT (43 Vassar Street, Cambridge, 02139 MA)
Speaker: Yang Zhou, Ph.D.
Affiliation: Research Scientist, Guoping Feng Lab, McGovern Institute for Brain Research, MIT
Talk title: Searching the Neural Basis of ASD from Genetically Engineered Model Systems
Abstract: Progress in understanding the neural basis of ASD is inspiring yet unsubstantial over the past decade, in part due to the lack of reliable model systems. Recapitulating core cognitive and behavioral dysfunctions which are closer and relevant to affected human individuals represents one of the significant challenges. Deletion or point mutation of synaptic genes, such as SHANK3 are frequently identified from idiopathic human ASD, allowing for the creation of engineered model systems with which to uncover the molecular, cellular pathophysiology and decipher the neural signature underlying ASD. I will report our efforts in developing advanced ASD models using cutting-edge genetic technologies and discuss behavioral as well as neural circuit alterations identified from models with the Shank3 mutation. We anticipate that our research will provide a critical step forward in the discovery of translatable biomarkers, as well as developing and testing of therapeutic strategies for ASD.

SCSB Lunch Series: Jakob Voigts, Ph.D.
2018-10-19 12:00 - 13:00 | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, October 19, 2018
Time: 12:00pm – 1:00pm
Location: Simons Center Conference Room, Building 46, Room 6011, 6th Floor, MIT (43 Vassar Street, Cambridge, 02139 MA)
Speaker: Jakob Voigts, Ph.D.
Affiliation: Simons Fellow, Mark Harnett Lab, MIT
Talk title: Dendritic mechanisms for navigation in retrosplenial cortex
Abstract: Navigation requires associating different streams of information. For example, recognizing a distant skyscraper while facing north vs. facing south has different interpretations for one’s position. Retrosplenial cortex, thought to be the main hub for carrying out such associations during navigation, is well suited to testing how individual neurons can flexibly combine multiple inputs to implement such computations. I will present results using recently developed technology that allows us to combine, for the first time, 2-D navigation with head rotation and conventional 2-photon imaging of dendrites. My findings show that dendritic activity is less modulated by context than the somatic outputs of neurons, suggesting that head-direction input is processed by active dendritic mechanisms. I will discuss how this approach can be used to study the link between within-neuron and network computations in general associative cortical computations.

SCSB Lunch Series: Rogier Landman, Ph.D.
2018-11-16 12:00 - 13:00 | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, November 16, 2018
Time: 12:00pm – 1:00pm
Location: Simons Center Conference Room, Building 46, Room 6011, 6th Floor, MIT (43 Vassar Street, Cambridge, 02139 MA)
Speaker: Rogier Landman, Ph.D.
Affiliation: Research Affiliate, McGovern Institute for Brain Research, MIT
Talk title: Behavioral characterization of non-human primates for autism research
Abstract: Disruption of the Shank3 gene has been implicated as a monogenic cause of Autism Spectrum Disorders. Although rare in humans, understanding how this mutation leads to symptoms could ultimately reveal how genetic factors in general affect the likelihood of autism. I will talk about behavior of a small group of CRISPR/Cas9 generated Shank3 mutant macaque monkeys using behavior scoring, eye tracking, movement tracking and social interaction. To analyze future genetic models in the common marmoset we have developed assays including eye tracking, automated movement and vocalization tracking, infant neurobehavioral screening, in-cage training and awake fMRI training.
Bio: Rogier Landman got his PhD at the University of Amsterdam, The Netherlands. He has investigated the neuronal mechanisms of visual attention and the influence of social stimuli on attentional capture. His current work involves automated behavioral monitoring and analysis of macaque and marmoset monkeys in the context of autism and schizophrenia.

SCSB Lunch Series: Guoping Feng, Ph.D.
2018-12-14 12:00 - 13:00 | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, December 14, 2018
Time: 12:00pm – 1:00pm
Location: Simons Center Conference Room, Building 46, Room 6011, 6th Floor, MIT (43 Vassar Street, Cambridge, 02139 MA)
Speaker: Guoping Feng, Ph.D.
Affiliation: Poitras Chair Professor of Neuroscience, McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, MIT; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard.
Talk title: Thalamic reticular nucleus dysfunction in neurodevelopmental disorders
Abstract: The Thalamic reticular nucleus (TRN) provides major inhibitory inputs to the thalamus and plays important roles in sensory gating, attention selection and sleep rhythms. Many of the risk genes for ASD, schizophrenia and ADHD are highly expressed in the TRN, raising the possibility that TRN may be a circuit converging point for some of the overlapping behavioral abnormalities in these disorders. Using TRN-specific genetic deletions in mice, we demonstrate the critical roles of TRN dysfunction in attention deficit, hyperactivity and sleep disruption, commonly observed in neurodevelopmental disorders including ASD. Using multi-scale single cell analysis including single cell RNA-Seq, multiplex RNA FISH, electrophysiological recordings and molecular tracing. We identified two major TRN neuronal subtypes that have distinct electrophysiological properties, differential topographic connectivity related to different thalamic sensory modalities, i.e. first order and high order thalamic nuclei. Through such non-overlapping anatomical pathways mediated by its subpopulations, TRN might differentially tune incoming sensory information through thalamo-cortical circuits. Importantly, we identified genes selectively expressed by each of the TRN subtypes of neurons, paving the way for testing molecular targets that could potentially regulate different TRN functions based on their thalamic connectivity.

SCSB Lunch Series: Nan Li, Ph.D.
2019-02-08 12:00 - 13:00 | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, February 8, 2019
Time: 12:00pm – 1:00pm
Location: Simons Center Conference Room, Building 46, Room 6011, 6th Floor, MIT (43 Vassar Street, Cambridge, 02139 MA)
Speaker: Nan Li, Ph.D.
Affiliation: Postdoctoral Fellow, Alan Jasanoff Laboratory, MIT
Talk title: Toward functional and molecular neuroimaging analysis of marmoset models
Abstract: Neurodevelopmental disorders affect many aspects of brain function, and surveying phenotypic abnormalities across altered brains can be challenging. Our group has created a suite of novel tools that can probe molecular-level hallmarks of brain function by magnetic resonance imaging (MRI), potentially enabling qualitatively new and mechanistically informative approaches to the analysis of brain-wide dysfunction in autism and other conditions. Here I will present our recently developed molecular imaging approaches for mapping spatiotemporal dynamics of diverse neural signaling components, including dopamine release and calcium signaling. Initial application of these tools has taken place in rodents, but we expect our molecular imaging methods to be of outstanding utility for whole-brain functional analysis of emerging primate disease models. I discuss progress toward establishing fMRI in awake marmosets at MIT, with the future goal of applying novel functional and molecular imaging techniques to characterize marmoset models of autism spectrum disorders.

SCSB Lunch Series: Danielle Tomasello, Ph.D.
2019-02-22 12:00 - 13:00 | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, February 22, 2019
Time: 12:00pm – 1:00pm
Location: Please note the room change — the talk will occur in the McGovern Seminar Room — 46-3189.
Speaker: Danielle Tomasello, Ph.D.
Affiliation: Simons Postdoctoral Fellow, Hazel Sive Laboratory, Whitehead Institute for Biomedical Research.
Talk title: FAM57B Ceramide Synthase, a Hub Gene within 16p11.2 Deletion Syndrome, Maintains Physiological Lipid Membrane Composition
Abstract: The genetic basis for mental health disorders is complex, making diagnostics unreliable and personalized treatments complex. My studies are aimed to address this challenge with a new approach to identify molecular changes in 16p11.2 deletion syndrome. In this prevalent syndrome (occurring in 1 in 2000 individuals) part of chromosome 16 is lost, encompassing a core of 25 genes. Deletion leads to severe brain symptoms including autism, intellectual disability and epilepsy. We hypothesize that the metabolome of neurons is abnormal in individuals with 16p11.2 deletion syndrome, providing a new approach to dissect this complex syndrome. I have concentrated on FAM57B, previously shown to interact with other enzyme-encoded genes within the interval, encoding a ceramide synthase. Consistent with altered metabolism in 16p11.2 deletion syndrome, we see profound changes in lipids in the zebrafish model and in 16p11.2 deletion fibroblasts. fam57b mutants show significant cellular and behavioral phenotypes, including lipid membrane disruption, reduced firing in whole brain recordings and behavioral deficits. We propose FAM57B is a critical protein essential for membrane lipid homeostasis, suggesting haploinsufficiency leads to a cascade of biochemical and cellular changes.

SCSB Lunch Series: Nancy Padilla, Ph.D.
2019-03-22 12:00 - 13:00 | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, March 22, 2019
Time: 12:00pm – 1:00pm
Location: Simons Center Conference Room, Building 46, Room 6011, 6th Floor, MIT (43 Vassar Street, Cambridge, 02139 MA)
Speaker: Nancy Padilla, Ph.D.
Affiliation: Simons Postdoctoral Fellow, Kay Tye Laboratory, Picower Institute of Learning and Memory, MIT.
Talk title: Investigating the neural circuits underlying social dominance in mice
Abstract: Most animals live in groups organized by social hierarchies. By acting according to their social rank, animals decrease unnecessary aggression and save energy. Although hierarchies are central to successful group dynamics, the neural basis of dominance behaviors remains unknown. Cross-species evidence suggests that the medial prefrontal cortex (mPFC) is crucial for social dominance behaviors. Given the role of the lateral hypothalamus (LH) in innate behaviors, and its connectivity with the mPFC, it is well positioned to modulate social behaviors in a rank-dependent manner. Using a reward competition assay, wireless electrophysiology and optogenetics in mice I am investigating the role of mPFC-LH pathway in social dominance. I will present data that suggest that the mPFC-LH drives winning during social competition.

SCSB Lunch Series: Michael Halassa, M.D., Ph.D.
2019-04-12 12:00 - 13:00 | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, April 12, 2019
Time: 12:00pm – 1:00pm
Location: Simons Center Conference Room, Building 46, Room 6011, 6th Floor, MIT (43 Vassar Street, Cambridge, 02139 MA)
Speaker: Michael Halassa, M.D., Ph.D.
Affiliation: Assistant Professor, Department of Brain and Cognitive Sciences, MIT.
Talk title: Frontothalamic interactions in cognitive control and flexibility
Abstract: Interactions between the cortex and thalamus are critical for sensation, action and cognition. However, most of our understanding of these interactions is in the context of sensory processing. My lab has focused on cortico-thalamic loops that are non-sensory, allowing us to discover new principles of thalamo-cortical interactions beyond sensory processing. In my talk, I will show how the thalamus plays previously unrecognized roles in implementing cognitive control and flexibility, which involve rapid reconfiguration of task-relevant prefrontal representations. I will give a few examples of this process, showing its generality across multiple species, and if time allows, discuss its relevance to disease processes.

SCSB Lunch Series: Anila D'Mello, Ph.D.
2019-05-10 12:00 - 13:00 | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, May 10, 2019
Time: 12:00pm – 1:00pm
Location: Simons Center Conference Room, Building 46, Room 6011, 6th Floor, MIT (43 Vassar Street, Cambridge, 02139 MA)
Speaker: Anila D’Mello Ph.D.
Affiliation: Simons Fellow, John Gabrieli Laboratory, McGovern Institute for Brain Research, MIT.
Talk title: Characterizing Neural Adaptation in Autism Spectrum Disorder
Abstract: Sensory processing difficulties occur in about 90% of individuals with Autism Spectrum Disorder (ASD). Sensory hypersensitivities may negatively affect sleep, communication, and contribute to impairments in social interaction. Recent evidence suggests that sensory hypersensitivies in ASD may be associated with challenges in rapidly adapting to regularities in the environment. Here, I will discuss our work using functional magnetic resonance imaging (fMRI) to measure neural adaptation across social and non-social domains in adults with and without a diagnosis of autism. Our preliminary findings suggest that neural adaptation may be associated with autistic traits and symptom severity.

SCSB Lunch Series – Hector Penagos, Ph.D.
2019-09-06 12:00 - 13:00 | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, September 6, 2019
Time: 12:00pm – 1:00pm
Location: Simons Center Conference Room, Building 46, Room 6011, 6th Floor, MIT (43 Vassar Street, Cambridge, 02139 MA)
Speaker: Hector Penagos, Ph.D.
Affiliation: Research Scientist, Wilson Laboratory, Picower Institute for Learning and Memory, MIT
Talk title: “Assessing thalamic participation in a joint hippocampus-retrosplenial cortex offline state ”
Abstract: The hippocampus and retrosplenial cortex have been implicated in a range of cognitive functions including navigation, planning and imagination. We recently discovered that the rodent hippocampus and retrosplenial cortex jointly transition into an offline state in response to increases in reward during spatial navigation tasks. At the neuronal ensemble level, this joint state is characterized by the reactivation of hippocampal spiking patterns linked to recent experiences. At the network level, both brain areas express oscillations previously thought to occur exclusively during sleep. This synchronous co-occurrence of sleep rhythms, along with the known role of the thalamus in sleep oscillations, raises the possibility that the thalamus might be involved in the generation of this waking state. In this talk, I will describe results that implicate the thalamic reticular nucleus in this hippocampal-retrosplenial offline state. These results extend the well-known role of the thalamus in coordinating activities across brain regions in sleep to the waking state.

SCSB Lunch Series – Sasha Krol, Ph.D.
2019-09-27 12:00 - 13:00 | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, September 27, 2019
Time: 12:00pm – 1:00pm
Location: Simons Center Conference Room, Building 46, Room 6011, 6th Floor, MIT (43 Vassar Street, Cambridge, 02139 MA)
Speaker: Sasha Krol, Ph.D.
Affiliation: Simons Fellow, Guoping Feng Laboratory, McGovern Institute for Brain Research, MIT.
Talk title: “Uncovering the origins of autism risk gene Ptchd1-associated aggression”
Abstract: Irritability or aggressive conduct affects 25-50% of children with autism spectrum disorder (ASD). Despite being highly disruptive, aggression in the context of ASD is poorly understood due to a lack of good models. Deletions in PTCHD1 contribute to ~1% of ASD cases with intellectual disability and can lead to hyper-aggression. I will present our work seeking to understand the origin of hyper-aggression in a mouse model of Ptchd1 deletion. We are testing whether dysfunction of hypothalamic circuitry, and in particular the VMHvl is responsible for Ptchd1-mediated, ASD-related aggression. We find that specifically inhibitory circuitry and not excitatory contributes to hyper-aggression. In addition we will present preliminary findings on the cellular function of Ptchd1.

SCSB Lunch Series: Oliver Saunders Wilder, Ph.D.
2019-10-25 12:00 - 13:00 | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, October 25, 2019
Time: 12:00pm – 1:00pm
Location: Simons Center Conference Room, Building 46, Room 6011, 6th Floor, MIT (43 Vassar Street, Cambridge, 02139 MA)
Speaker: Oliver Saunders Wilder, Ph.D.
Affiliation: Research Affiliate at the MIT Media Lab & Lead Technologist at Tools of the Mind.
Talk title: Using Interpersonal Physiology to Measure Socio-affective Dynamics: Techniques, Findings, and Opportunities
Abstract: Individuals with Autism Spectrum Disorder (ASD) often have great difficulty interpreting and using nonverbal communication, understanding and navigating social relationships, and making sense of their own and others’ emotions. Many of these challenges can be understood in terms of difficulty with social reciprocity, the ability to attend to, predict, and respond appropriately to the mental states of others, and are present in both more severely affected as well as “higher-functioning” individuals with ASD who have little or no cognitive impairment. A key challenge to studying the development of social reciprocity is that social interactions are fundamentally transactional, taking place within a system rather than in isolation, and that people affect and are affected by their interactions with others. A growing body of work in interpersonal physiology – the study of psychophysiological signals across two or more people – can offer a powerful new means for non-invasive ambulatory assessment of socio-affective processes in a variety of laboratory and naturalistic settings. I will present a novel statistical modeling technique for quantifying interpersonal physiology, and discuss several applications of this technique, including a study of young children with and without an autism diagnosis and their parent, a pilot study of pre-term infants and caregivers in a neonatal intensive care unit, and a clinical application our new real-time physiological synchrony system for interpersonal biofeedback in mental health counseling.
Click here for CV.

SCSB Lunch Series: Dara S. Manoach, Ph.D.
2019-11-08 12:00 - 13:00 | Simons Center Conference Room, Bldg. 46, Room 6011, 43 Vassar Street, Cambridge, MA, 02139, United States
Date: Friday, November 8, 2019
Time: 12:00pm – 1:00pm
Location: Simons Center Conference Room, Building 46, Room 6011, 6th Floor, MIT (43 Vassar Street, Cambridge, 02139 MA)
Speaker: Dara S. Manoach, Ph.D.
Affiliation: Professor of Psychology, Department of Psychiatry at Harvard Medical School.
Talk title: Targeting sleep oscillations to improve cognition in neurodevelopmental disorders.
Abstract: Sleep oscillations are novel pathophysiological targets for therapy to improve cognition. This talk will summarize our understanding of how sleep oscillations interact to consolidate memory and illustrate this with findings from our recent clinical trial in schizophrenia and ongoing studies of autism spectrum disorder. Finally, I will present pilot data from a study of auditory stimulation during sleep to improve memory. Our findings demonstrate that effective therapies will need to enhance sleep oscillatory dynamics and restore function at the network level.
