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  1. Book ; Online: Behavior quantification as the missing link between fields

    Ennis, Michaela

    Tools for digital psychiatry and their role in the future of neurobiology

    2023  

    Abstract: The great behavioral heterogeneity observed between individuals with the same psychiatric disorder and even within one individual over time complicates both clinical practice and biomedical research. However, modern technologies are an exciting ... ...

    Abstract The great behavioral heterogeneity observed between individuals with the same psychiatric disorder and even within one individual over time complicates both clinical practice and biomedical research. However, modern technologies are an exciting opportunity to improve behavioral characterization. Existing psychiatry methods that are qualitative or unscalable, such as patient surveys or clinical interviews, can now be collected at a greater capacity and analyzed to produce new quantitative measures. Furthermore, recent capabilities for continuous collection of passive sensor streams, such as phone GPS or smartwatch accelerometer, open avenues of novel questioning that were previously entirely unrealistic. Their temporally dense nature enables a cohesive study of real-time neural and behavioral signals. To develop comprehensive neurobiological models of psychiatric disease, it will be critical to first develop strong methods for behavioral quantification. There is huge potential in what can theoretically be captured by current technologies, but this in itself presents a large computational challenge -- one that will necessitate new data processing tools, new machine learning techniques, and ultimately a shift in how interdisciplinary work is conducted. In my thesis, I detail research projects that take different perspectives on digital psychiatry, subsequently tying ideas together with a concluding discussion on the future of the field. I also provide software infrastructure where relevant, with extensive documentation. Major contributions include scientific arguments and proof of concept results for daily free-form audio journals as an underappreciated psychiatry research datatype, as well as novel stability theorems and pilot empirical success for a proposed multi-area recurrent neural network architecture.

    Comment: PhD thesis copy
    Keywords Quantitative Biology - Neurons and Cognition ; Computer Science - Artificial Intelligence ; Computer Science - Computers and Society
    Subject code 020
    Publishing date 2023-05-24
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Book ; Online: Contraction Properties of the Global Workspace Primitive

    Ennis, Michaela / Kozachkov, Leo / Slotine, Jean-Jacques

    2023  

    Abstract: To push forward the important emerging research field surrounding multi-area recurrent neural networks (RNNs), we expand theoretically and empirically on the provably stable RNNs of RNNs introduced by Kozachkov et al. in "RNNs of RNNs: Recursive ... ...

    Abstract To push forward the important emerging research field surrounding multi-area recurrent neural networks (RNNs), we expand theoretically and empirically on the provably stable RNNs of RNNs introduced by Kozachkov et al. in "RNNs of RNNs: Recursive Construction of Stable Assemblies of Recurrent Neural Networks". We prove relaxed stability conditions for salient special cases of this architecture, most notably for a global workspace modular structure. We then demonstrate empirical success for Global Workspace Sparse Combo Nets with a small number of trainable parameters, not only through strong overall test performance but also greater resilience to removal of individual subnetworks. These empirical results for the global workspace inter-area topology are contingent on stability preservation, highlighting the relevance of our theoretical work for enabling modular RNN success. Further, by exploring sparsity in the connectivity structure between different subnetwork modules more broadly, we improve the state of the art performance for stable RNNs on benchmark sequence processing tasks, thus underscoring the general utility of specialized graph structures for multi-area RNNs.
    Keywords Computer Science - Machine Learning ; Electrical Engineering and Systems Science - Systems and Control ; Quantitative Biology - Neurons and Cognition
    Subject code 629
    Publishing date 2023-10-02
    Publishing country us
    Document type Book ; Online
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  3. Article ; Online: Linguistic and non-linguistic markers of disorganization in psychotic illness.

    Liebenthal, Einat / Ennis, Michaela / Rahimi-Eichi, Habiballah / Lin, Eric / Chung, Yoonho / Baker, Justin T

    Schizophrenia research

    2022  Volume 259, Page(s) 111–120

    Abstract: Background: Disorganization, presenting as impairment in thought, language and goal-directed behavior, is a core multidimensional syndrome of psychotic disorders. This study examined whether scalable computational measures of spoken language, and ... ...

    Abstract Background: Disorganization, presenting as impairment in thought, language and goal-directed behavior, is a core multidimensional syndrome of psychotic disorders. This study examined whether scalable computational measures of spoken language, and smartphone usage pattern, could serve as digital biomarkers of clinical disorganization symptoms.
    Methods: We examined in a longitudinal cohort of adults with a psychotic disorder, the associations between clinical measures of disorganization and computational measures of 1) spoken language derived from monthly, semi-structured, recorded clinical interviews; and 2) smartphone usage pattern derived via passive sensing technologies over the month prior to the interview. The language features included speech quantity, rate, fluency, and semantic regularity. The smartphone features included data missingness and phone usage during sleep time. The clinical measures consisted of the Positive and Negative Symptom Scale (PANSS) conceptual disorganization, difficulty in abstract thinking, and poor attention, items. Mixed linear regression analyses were used to estimate both fixed and random effects.
    Results: Greater severity of clinical symptoms of conceptual disorganization was associated with greater verbosity and more disfluent speech. Greater severity of conceptual disorganization was also associated with greater missingness of smartphone data, and greater smartphone usage during sleep time. While the observed associations were significant across the group, there was also significant variation between individuals.
    Conclusions: The findings suggest that digital measures of speech disfluency may serve as scalable markers of conceptual disorganization. The findings warrant further investigation into the use of recorded interviews and passive sensing technologies to assist in the characterization and tracking of psychotic illness.
    MeSH term(s) Adult ; Humans ; Psychotic Disorders/diagnosis ; Language ; Thinking ; Cognition ; Speech
    Language English
    Publishing date 2022-12-21
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 639422-x
    ISSN 1573-2509 ; 0920-9964
    ISSN (online) 1573-2509
    ISSN 0920-9964
    DOI 10.1016/j.schres.2022.12.003
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  4. Book ; Online: RNNs of RNNs

    Kozachkov, Leo / Ennis, Michaela / Slotine, Jean-Jacques

    Recursive Construction of Stable Assemblies of Recurrent Neural Networks

    2021  

    Abstract: Recurrent neural networks (RNNs) are widely used throughout neuroscience as models of local neural activity. Many properties of single RNNs are well characterized theoretically, but experimental neuroscience has moved in the direction of studying ... ...

    Abstract Recurrent neural networks (RNNs) are widely used throughout neuroscience as models of local neural activity. Many properties of single RNNs are well characterized theoretically, but experimental neuroscience has moved in the direction of studying multiple interacting areas, and RNN theory needs to be likewise extended. We take a constructive approach towards this problem, leveraging tools from nonlinear control theory and machine learning to characterize when combinations of stable RNNs will themselves be stable. Importantly, we derive conditions which allow for massive feedback connections between interacting RNNs. We parameterize these conditions for easy optimization using gradient-based techniques, and show that stability-constrained "networks of networks" can perform well on challenging sequential-processing benchmark tasks. Altogether, our results provide a principled approach towards understanding distributed, modular function in the brain.

    Comment: Published as a conference paper at NeurIPS 2022
    Keywords Computer Science - Machine Learning ; Mathematics - Dynamical Systems ; Quantitative Biology - Neurons and Cognition
    Subject code 006
    Publishing date 2021-06-16
    Publishing country us
    Document type Book ; Online
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  5. Article ; Online: Neuronal deletion of Gtf2i, associated with Williams syndrome, causes behavioral and myelin alterations rescuable by a remyelinating drug.

    Barak, Boaz / Zhang, Zicong / Liu, Yuanyuan / Nir, Ariel / Trangle, Sari S / Ennis, Michaela / Levandowski, Kirsten M / Wang, Dongqing / Quast, Kathleen / Boulting, Gabriella L / Li, Yi / Bayarsaihan, Dashzeveg / He, Zhigang / Feng, Guoping

    Nature neuroscience

    2019  Volume 22, Issue 5, Page(s) 700–708

    Abstract: Williams syndrome (WS), caused by a heterozygous microdeletion on chromosome 7q11.23, is a neurodevelopmental disorder characterized by hypersociability and neurocognitive abnormalities. Of the deleted genes, general transcription factor IIi (Gtf2i) has ... ...

    Abstract Williams syndrome (WS), caused by a heterozygous microdeletion on chromosome 7q11.23, is a neurodevelopmental disorder characterized by hypersociability and neurocognitive abnormalities. Of the deleted genes, general transcription factor IIi (Gtf2i) has been linked to hypersociability in WS, although the underlying mechanisms are poorly understood. We show that selective deletion of Gtf2i in the excitatory neurons of the forebrain caused neuroanatomical defects, fine motor deficits, increased sociability and anxiety. Unexpectedly, 70% of the genes with significantly decreased messenger RNA levels in the mutant mouse cortex are involved in myelination, and mutant mice had reduced mature oligodendrocyte cell numbers, reduced myelin thickness and impaired axonal conductivity. Restoring myelination properties with clemastine or increasing axonal conductivity rescued the behavioral deficits. The frontal cortex from patients with WS similarly showed reduced myelin thickness, mature oligodendrocyte cell numbers and mRNA levels of myelination-related genes. Our study provides molecular and cellular evidence for myelination deficits in WS linked to neuronal deletion of Gtf2i.
    MeSH term(s) Animals ; Axons/drug effects ; Behavior, Animal ; Clemastine/administration & dosage ; Male ; Mice, Inbred C57BL ; Mice, Transgenic ; Motor Skills ; Myelin Sheath/metabolism ; Myelin Sheath/ultrastructure ; Neurons/metabolism ; Prosencephalon/metabolism ; Remyelination/drug effects ; Social Behavior ; Transcription Factors, TFII/genetics ; Transcriptome ; Williams Syndrome/genetics
    Chemical Substances Gtf2i protein, mouse ; Transcription Factors, TFII ; Clemastine (95QN29S1ID)
    Language English
    Publishing date 2019-04-22
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1420596-8
    ISSN 1546-1726 ; 1097-6256
    ISSN (online) 1546-1726
    ISSN 1097-6256
    DOI 10.1038/s41593-019-0380-9
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  6. Article ; Online: Publisher Correction: Neuronal deletion of Gtf2i, associated with Williams syndrome, causes behavioral and myelin alterations rescuable by a remyelinating drug.

    Barak, Boaz / Zhang, Zicong / Liu, Yuanyuan / Nir, Ariel / Trangle, Sari S / Ennis, Michaela / Levandowski, Kirsten M / Wang, Dongqing / Quast, Kathleen / Boulting, Gabriella L / Li, Yi / Bayarsaihan, Dashzeveg / He, Zhigang / Feng, Guoping

    Nature neuroscience

    2019  Volume 22, Issue 7, Page(s) 1197

    Abstract: The original and corrected figures are shown in the accompanying Publisher Correction. ...

    Abstract The original and corrected figures are shown in the accompanying Publisher Correction.
    Language English
    Publishing date 2019-06-06
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 1420596-8
    ISSN 1546-1726 ; 1097-6256
    ISSN (online) 1546-1726
    ISSN 1097-6256
    DOI 10.1038/s41593-019-0441-0
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  7. Article: Case Report of Dual-Site Neurostimulation and Chronic Recording of Cortico-Striatal Circuitry in a Patient With Treatment Refractory Obsessive Compulsive Disorder.

    Olsen, Sarah T / Basu, Ishita / Bilge, Mustafa Taha / Kanabar, Anish / Boggess, Matthew J / Rockhill, Alexander P / Gosai, Aishwarya K / Hahn, Emily / Peled, Noam / Ennis, Michaela / Shiff, Ilana / Fairbank-Haynes, Katherine / Salvi, Joshua D / Cusin, Cristina / Deckersbach, Thilo / Williams, Ziv / Baker, Justin T / Dougherty, Darin D / Widge, Alik S

    Frontiers in human neuroscience

    2020  Volume 14, Page(s) 569973

    Abstract: Psychiatric disorders are increasingly understood as dysfunctions of hyper- or hypoconnectivity in distributed brain circuits. A prototypical example is obsessive compulsive disorder (OCD), which has been repeatedly linked to hyper-connectivity of ... ...

    Abstract Psychiatric disorders are increasingly understood as dysfunctions of hyper- or hypoconnectivity in distributed brain circuits. A prototypical example is obsessive compulsive disorder (OCD), which has been repeatedly linked to hyper-connectivity of cortico-striatal-thalamo-cortical (CSTC) loops. Deep brain stimulation (DBS) and lesions of CSTC structures have shown promise for treating both OCD and related disorders involving over-expression of automatic/habitual behaviors. Physiologically, we propose that this CSTC hyper-connectivity may be reflected in high synchrony of neural firing between loop structures, which could be measured as coherent oscillations in the local field potential (LFP). Here we report the results from the pilot patient in an Early Feasibility study (https://clinicaltrials.gov/ct2/show/NCT03184454) in which we use the Medtronic Activa PC+ S device to simultaneously record and stimulate in the supplementary motor area (SMA) and ventral capsule/ventral striatum (VC/VS). We hypothesized that frequency-mismatched stimulation should disrupt coherence and reduce compulsive symptoms. The patient reported subjective improvement in OCD symptoms and showed evidence of improved cognitive control with the addition of cortical stimulation, but these changes were not reflected in primary rating scales specific to OCD and depression, or during blinded cortical stimulation. This subjective improvement was correlated with increased SMA and VC/VS coherence in the alpha, beta, and gamma bands, signals which persisted after correcting for stimulation artifacts. We discuss the implications of this research, and propose future directions for research in network modulation in OCD and more broadly across psychiatric disorders.
    Language English
    Publishing date 2020-10-23
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2425477-0
    ISSN 1662-5161
    ISSN 1662-5161
    DOI 10.3389/fnhum.2020.569973
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  8. Article ; Online: Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ): Rationale and Study Design of the Largest Global Prospective Cohort Study of Clinical High Risk for Psychosis.

    Wannan, Cassandra M J / Nelson, Barnaby / Addington, Jean / Allott, Kelly / Anticevic, Alan / Arango, Celso / Baker, Justin T / Bearden, Carrie E / Billah, Tashrif / Bouix, Sylvain / Broome, Matthew R / Buccilli, Kate / Cadenhead, Kristin S / Calkins, Monica E / Cannon, Tyrone D / Cecci, Guillermo / Chen, Eric Yu Hai / Cho, Kang Ik K / Choi, Jimmy /
    Clark, Scott R / Coleman, Michael J / Conus, Philippe / Corcoran, Cheryl M / Cornblatt, Barbara A / Diaz-Caneja, Covadonga M / Dwyer, Dominic / Ebdrup, Bjørn H / Ellman, Lauren M / Fusar-Poli, Paolo / Galindo, Liliana / Gaspar, Pablo A / Gerber, Carla / Glenthøj, Louise Birkedal / Glynn, Robert / Harms, Michael P / Horton, Leslie E / Kahn, René S / Kambeitz, Joseph / Kambeitz-Ilankovic, Lana / Kane, John M / Kapur, Tina / Keshavan, Matcheri S / Kim, Sung-Wan / Koutsouleris, Nikolaos / Kubicki, Marek / Kwon, Jun Soo / Langbein, Kerstin / Lewandowski, Kathryn E / Light, Gregory A / Mamah, Daniel / Marcy, Patricia J / Mathalon, Daniel H / McGorry, Patrick D / Mittal, Vijay A / Nordentoft, Merete / Nunez, Angela / Pasternak, Ofer / Pearlson, Godfrey D / Perez, Jesus / Perkins, Diana O / Powers, Albert R / Roalf, David R / Sabb, Fred W / Schiffman, Jason / Shah, Jai L / Smesny, Stefan / Spark, Jessica / Stone, William S / Strauss, Gregory P / Tamayo, Zailyn / Torous, John / Upthegrove, Rachel / Vangel, Mark / Verma, Swapna / Wang, Jijun / Rossum, Inge Winter-van / Wolf, Daniel H / Wolff, Phillip / Wood, Stephen J / Yung, Alison R / Agurto, Carla / Alvarez-Jimenez, Mario / Amminger, Paul / Armando, Marco / Asgari-Targhi, Ameneh / Cahill, John / Carrión, Ricardo E / Castro, Eduardo / Cetin-Karayumak, Suheyla / Mallar Chakravarty, M / Cho, Youngsun T / Cotter, David / D'Alfonso, Simon / Ennis, Michaela / Fadnavis, Shreyas / Fonteneau, Clara / Gao, Caroline / Gupta, Tina / Gur, Raquel E / Gur, Ruben C / Hamilton, Holly K / Hoftman, Gil D / Jacobs, Grace R / Jarcho, Johanna / Ji, Jie Lisa / Kohler, Christian G / Lalousis, Paris Alexandros / Lavoie, Suzie / Lepage, Martin / Liebenthal, Einat / Mervis, Josh / Murty, Vishnu / Nicholas, Spero C / Ning, Lipeng / Penzel, Nora / Poldrack, Russell / Polosecki, Pablo / Pratt, Danielle N / Rabin, Rachel / Rahimi Eichi, Habiballah / Rathi, Yogesh / Reichenberg, Avraham / Reinen, Jenna / Rogers, Jack / Ruiz-Yu, Bernalyn / Scott, Isabelle / Seitz-Holland, Johanna / Srihari, Vinod H / Srivastava, Agrima / Thompson, Andrew / Turetsky, Bruce I / Walsh, Barbara C / Whitford, Thomas / Wigman, Johanna T W / Yao, Beier / Yuen, Hok Pan / Ahmed, Uzair / Byun, Andrew Jin Soo / Chung, Yoonho / Do, Kim / Hendricks, Larry / Huynh, Kevin / Jeffries, Clark / Lane, Erlend / Langholm, Carsten / Lin, Eric / Mantua, Valentina / Santorelli, Gennarina / Ruparel, Kosha / Zoupou, Eirini / Adasme, Tatiana / Addamo, Lauren / Adery, Laura / Ali, Munaza / Auther, Andrea / Aversa, Samantha / Baek, Seon-Hwa / Bates, Kelly / Bathery, Alyssa / Bayer, Johanna M M / Beedham, Rebecca / Bilgrami, Zarina / Birch, Sonia / Bonoldi, Ilaria / Borders, Owen / Borgatti, Renato / Brown, Lisa / Bruna, Alejandro / Carrington, Holly / Castillo-Passi, Rolando I / Chen, Justine / Cheng, Nicholas / Ching, Ann Ee / Clifford, Chloe / Colton, Beau-Luke / Contreras, Pamela / Corral, Sebastián / Damiani, Stefano / Done, Monica / Estradé, Andrés / Etuka, Brandon Asika / Formica, Melanie / Furlan, Rachel / Geljic, Mia / Germano, Carmela / Getachew, Ruth / Goncalves, Mathias / Haidar, Anastasia / Hartmann, Jessica / Jo, Anna / John, Omar / Kerins, Sarah / Kerr, Melissa / Kesselring, Irena / Kim, Honey / Kim, Nicholas / Kinney, Kyle / Krcmar, Marija / Kotler, Elana / Lafanechere, Melanie / Lee, Clarice / Llerena, Joshua / Markiewicz, Christopher / Matnejl, Priya / Maturana, Alejandro / Mavambu, Aissata / Mayol-Troncoso, Rocío / McDonnell, Amelia / McGowan, Alessia / McLaughlin, Danielle / McIlhenny, Rebecca / McQueen, Brittany / Mebrahtu, Yohannes / Mensi, Martina / Hui, Christy Lai Ming / Suen, Yi Nam / Wong, Stephanie Ming Yin / Morrell, Neal / Omar, Mariam / Partridge, Alice / Phassouliotis, Christina / Pichiecchio, Anna / Politi, Pierluigi / Porter, Christian / Provenzani, Umberto / Prunier, Nicholas / Raj, Jasmine / Ray, Susan / Rayner, Victoria / Reyes, Manuel / Reynolds, Kate / Rush, Sage / Salinas, Cesar / Shetty, Jashmina / Snowball, Callum / Tod, Sophie / Turra-Fariña, Gabriel / Valle, Daniela / Veale, Simone / Whitson, Sarah / Wickham, Alana / Youn, Sarah / Zamorano, Francisco / Zavaglia, Elissa / Zinberg, Jamie / Woods, Scott W / Shenton, Martha E

    Schizophrenia bulletin

    2024  Volume 50, Issue 3, Page(s) 496–512

    Abstract: This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of ... ...

    Abstract This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals.
    MeSH term(s) Humans ; Psychotic Disorders ; Schizophrenia ; Prospective Studies ; Adult ; Prodromal Symptoms ; Young Adult ; International Cooperation ; Adolescent ; Research Design/standards ; Male ; Female
    Language English
    Publishing date 2024-03-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 439173-1
    ISSN 1745-1701 ; 0586-7614
    ISSN (online) 1745-1701
    ISSN 0586-7614
    DOI 10.1093/schbul/sbae011
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