- Email: [email protected]
322. Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex: A Review of Methods and Utility in Psychiatry
Biological Psychiatry
Thursday Abstracts
Conclusions: Mood can be considered a memory stochastic process in HC, euthymic BD and their healthy first-degree relatives. Healthy relatives' measurements are "in between" those of BD and HC, which provides further insight into the nature of mood regulation in BD and supports the utility of nonlinear analyses in Psychiatry. Keywords: Mood, entropy, nonlinear
321. Watching Synapses in Action: From Assaying Synaptic Function to Drug Discovery Nachiket Kashikar, John Kemp, and Hilde Lavreysen Janssen Pharmaceutica N.V Background: Synaptic deficits in function and number are at the core of psychiatric and neurodegenerative diseases. The only way to alleviate the disease symptoms is by repairing the synaptic deficits and restoring functional connectivity of defined neuronal circuits. This requires monitoring and controlling the activity of thousands of synapses. Recent technological advances in the form of genetically-encoded sensors of neuronal activity, optogenetic actuators, and novel imaging methodologies make it now possible to record and manipulate the activity of neural circuits at exquisite spatiotemporal precision. Here we showcase our efforts towards bringing these breakthrough technologies in our drug discovery programmes. Methods: In a novel drug-screening platform, using rat neuronal cultures, we employ genetically-encoded sensors that allow us to record in real time synaptically localized Ca21 events, vesicle exo/endocytosis, and release of various neurotransmitters. We stimulate the cultures either by using a pair of electrodes or using channelrhodopsin in an all-optical approach. Using advanced image analysis software, we extract information about the activity of individual synapses within a population. Results: We employ this strategy to study the synaptic underpinnings of the cognitive and mnemonic frailty in Alzheimer’s disease and to find molecules that repair synaptic deficits. In particular, we show data in the context of discovering novel modulators of synaptic plasticity. Conclusions: In future, we will expand this technological approach to assay synaptic plasticity in human iPSC-derived neurons and ex vivo and in vivo in model systems of Alzheimer’s disease. The technology is amenable for translational use in the context of any psychiatric disease. Keywords: Alzheimer’s Disease, synaptic plasticity, calcium imaging, psychiatric disorders, in vitro
322. Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex: A Review of Methods and Utility in Psychiatry Andrew Olagunju, Scott Clark, and Bernhard Baune Discipline of Psychiatry, University of Adelaide Background: Transcranial magnetic stimulation (TMS) constitutes a major addition to the armamentarium of noninvasive investigative and treatment techniques for psychiatry
S132
disorders. There is evidence pointing to the potential role of TMS to elucidate biological markers of psychiatric disorders. Compared to the motor cortex, there is less use of TMS for functional assessment of non-motor cortical regions of the brain despite therapeutic applications of TMS on DLFC (a non-motor cortical area) in treat-resistant psychiatric disorders. Thus, we propose to review evidence on TMS paradigms focused on Dorsolateral Prefrontal Cortex (DLPFC) in major psychiatry disorders, and synthesize evidence on the application of TMS in neurobiological investigation underpinning these major psychiatry disorders especially neurocognitive functions. Methods: A comprehensive literature search and review based on the PRISMA approach was carried out using the following MeSH terms- “TMS”, “TMS-EEG“, “DLPFC”, “TMS’, “EEG’’, “Psychiatry disorders” and “Non-invasive brain stimulation”, "Neurocognitive", "Functional outcome" Results: There are known therapeutic applications of TMS on DLPFC (non-motor cortical area) in cases of treatresistant psychiatric disorders. A number of TMS paradigms have been used to investigate the neurobiological processes underlining the phenotypic expression, delayed treatment response and neurocognitive outcome of psychiatric disorders. Results from TMS have implicated non-motor cortical regions (DLPFC) in the pathophysiology of major psychiatric disorders, that include the neurocognitive dysfunctions often seen in these disorders despite treatment. Conclusions: The use of TMS on DLPFC supports its potential role in elucidating biological signature of psychiatric disorders, and the need to extend its use in investigative/translational Psychiatry, especially on the non-motor cortical regions. Keywords: Dorsolateral Prefrontal Cortex, Neurocognitive, Nonmotor cortex, Transcranial Magnetic Stimulation
323. Utilizing Smartphones to Collect Longitudinal Digital Phenotypes in Patients with Schizophrenia John Torous1, Patrick Staples2, Luis Sandoval1, Ian Barnett2, Jukka Pekka Onnela2, and Matcheri Keshavan1 1
Harvard Medical School, 2Harvard School of Public Health
Background: Digital phenotyping, the moment-by-moment quantification of the individual-level human phenotype using data from digital devices as proposed by JP Onnela, holds the potential to brings a steam of real time objective behavioral and physiological data into psychiatric research. In our ongoing study, we utilize the Beiwe platform to assess the feasibility and validity of passive data (GPS, accelerometer, voice, call logs, and text logs, screen use) from the personal smartphones of patients with schizophrenia as well as its utility in predicting relapse. Methods: Subjects are adults diagnosed with schizophrenia, currently in treatment at a state hospital. Subjects install Beiwe on their smartphone for three months. During this time Beiwe offers bi-weekly EMA surveys and constant passive data collection – up to one million data points per day via the phones many sensors. Results: From data pooled from all subjects 17 to date, the total duration of minutes not using the phone shows a negative correlation with the warning signs scale for psychosis (p5.0001)
Biological Psychiatry May 15, 2017; 81:S1–S139 www.sobp.org/journal
Thursday Abstracts
Conclusions: Mood can be considered a memory stochastic process in HC, euthymic BD and their healthy first-degree relatives. Healthy relatives' measurements are "in between" those of BD and HC, which provides further insight into the nature of mood regulation in BD and supports the utility of nonlinear analyses in Psychiatry. Keywords: Mood, entropy, nonlinear
321. Watching Synapses in Action: From Assaying Synaptic Function to Drug Discovery Nachiket Kashikar, John Kemp, and Hilde Lavreysen Janssen Pharmaceutica N.V Background: Synaptic deficits in function and number are at the core of psychiatric and neurodegenerative diseases. The only way to alleviate the disease symptoms is by repairing the synaptic deficits and restoring functional connectivity of defined neuronal circuits. This requires monitoring and controlling the activity of thousands of synapses. Recent technological advances in the form of genetically-encoded sensors of neuronal activity, optogenetic actuators, and novel imaging methodologies make it now possible to record and manipulate the activity of neural circuits at exquisite spatiotemporal precision. Here we showcase our efforts towards bringing these breakthrough technologies in our drug discovery programmes. Methods: In a novel drug-screening platform, using rat neuronal cultures, we employ genetically-encoded sensors that allow us to record in real time synaptically localized Ca21 events, vesicle exo/endocytosis, and release of various neurotransmitters. We stimulate the cultures either by using a pair of electrodes or using channelrhodopsin in an all-optical approach. Using advanced image analysis software, we extract information about the activity of individual synapses within a population. Results: We employ this strategy to study the synaptic underpinnings of the cognitive and mnemonic frailty in Alzheimer’s disease and to find molecules that repair synaptic deficits. In particular, we show data in the context of discovering novel modulators of synaptic plasticity. Conclusions: In future, we will expand this technological approach to assay synaptic plasticity in human iPSC-derived neurons and ex vivo and in vivo in model systems of Alzheimer’s disease. The technology is amenable for translational use in the context of any psychiatric disease. Keywords: Alzheimer’s Disease, synaptic plasticity, calcium imaging, psychiatric disorders, in vitro
322. Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex: A Review of Methods and Utility in Psychiatry Andrew Olagunju, Scott Clark, and Bernhard Baune Discipline of Psychiatry, University of Adelaide Background: Transcranial magnetic stimulation (TMS) constitutes a major addition to the armamentarium of noninvasive investigative and treatment techniques for psychiatry
S132
disorders. There is evidence pointing to the potential role of TMS to elucidate biological markers of psychiatric disorders. Compared to the motor cortex, there is less use of TMS for functional assessment of non-motor cortical regions of the brain despite therapeutic applications of TMS on DLFC (a non-motor cortical area) in treat-resistant psychiatric disorders. Thus, we propose to review evidence on TMS paradigms focused on Dorsolateral Prefrontal Cortex (DLPFC) in major psychiatry disorders, and synthesize evidence on the application of TMS in neurobiological investigation underpinning these major psychiatry disorders especially neurocognitive functions. Methods: A comprehensive literature search and review based on the PRISMA approach was carried out using the following MeSH terms- “TMS”, “TMS-EEG“, “DLPFC”, “TMS’, “EEG’’, “Psychiatry disorders” and “Non-invasive brain stimulation”, "Neurocognitive", "Functional outcome" Results: There are known therapeutic applications of TMS on DLPFC (non-motor cortical area) in cases of treatresistant psychiatric disorders. A number of TMS paradigms have been used to investigate the neurobiological processes underlining the phenotypic expression, delayed treatment response and neurocognitive outcome of psychiatric disorders. Results from TMS have implicated non-motor cortical regions (DLPFC) in the pathophysiology of major psychiatric disorders, that include the neurocognitive dysfunctions often seen in these disorders despite treatment. Conclusions: The use of TMS on DLPFC supports its potential role in elucidating biological signature of psychiatric disorders, and the need to extend its use in investigative/translational Psychiatry, especially on the non-motor cortical regions. Keywords: Dorsolateral Prefrontal Cortex, Neurocognitive, Nonmotor cortex, Transcranial Magnetic Stimulation
323. Utilizing Smartphones to Collect Longitudinal Digital Phenotypes in Patients with Schizophrenia John Torous1, Patrick Staples2, Luis Sandoval1, Ian Barnett2, Jukka Pekka Onnela2, and Matcheri Keshavan1 1
Harvard Medical School, 2Harvard School of Public Health
Background: Digital phenotyping, the moment-by-moment quantification of the individual-level human phenotype using data from digital devices as proposed by JP Onnela, holds the potential to brings a steam of real time objective behavioral and physiological data into psychiatric research. In our ongoing study, we utilize the Beiwe platform to assess the feasibility and validity of passive data (GPS, accelerometer, voice, call logs, and text logs, screen use) from the personal smartphones of patients with schizophrenia as well as its utility in predicting relapse. Methods: Subjects are adults diagnosed with schizophrenia, currently in treatment at a state hospital. Subjects install Beiwe on their smartphone for three months. During this time Beiwe offers bi-weekly EMA surveys and constant passive data collection – up to one million data points per day via the phones many sensors. Results: From data pooled from all subjects 17 to date, the total duration of minutes not using the phone shows a negative correlation with the warning signs scale for psychosis (p5.0001)
Biological Psychiatry May 15, 2017; 81:S1–S139 www.sobp.org/journal