Neuromodulation
neuromodulation
Dr. Fleur Zeldenrust
We are looking for a postdoctoral researcher to study the effects of neuromodulators in biologically realistic networks and learning tasks in the Vidi project 'Top-down neuromodulation and bottom-up network computation, a computational study'. You will use cellular and behavioural data gathered by our department over the previous five years on dopamine, acetylcholine and serotonin in mouse barrel cortex, to bridge the gap between single cell, network and behavioural effects. The aim of this project is to explain the effects of neuromodulation on task performance in biologically realistic spiking recurrent neural networks (SRNNs). You will use biologically realistic learning frameworks, such as force learning, to study how network structure influences task performance. You will use existing open source data to train a SRNN on a pole detection task (for rodents using their whiskers) and incorporate realistic network properties of the (barrel) cortex based on our lab's measurements. Next, you will incorporate the cellular effects of dopamine, acetylcholine and serotonin that we have measured into the network, and investigate their effects on task performance. In particular, you will research the effects of biologically realistic network properties (balance between excitation and inhibition and the resulting chaotic activity, non-linear neuronal input-output relations, patterns in connectivity, Dale's law) and incorporate known neuron and network effects. You will build on the single cell data, network models and analysis methods available in our group, and your results will be incorporated into our group's further research to develop and validate efficient coding models of (somatosensory) perception. We are therefore looking for a team player who can collaborate well with the other group members, and is willing to both learn from them and share their knowledge.
Dr. Alexander Herman
We seek a postdoc to work on an exciting federally funded project examining cognitive effort and flexibility in traumatic brain injury (TBI). This project will use a combination of transcranial alternating current stimulation and computational modeling to improve symptoms of mental fatigue after TBI. Our interdisciplinary, joint psychiatry-neurosurgery lab offers a unique opportunity to learn or improve skills in electrophysiology, non-invasive brain stimulation, neuroeconomics, and computational modeling. The ideal candidate has a background in both engineering/computer science and cognitive neuroscience or a strong willingness to learn one or the other. The position offers the opportunity to gain experience working with patients to collect data, but strong staff support exists for this already. The focus of the post-doc will be on analyzing data and writing papers. See our website at www.hermandarrowlab.com
Dr. Fleur Zeldenrust
We are looking for a postdoctoral researcher to work on the Vidi project 'Top-down neuromodulation and bottom-up network computation, a computational study' and study the effects of neuromodulators in balanced networks. You will use cellular and behavioural data on the effects of dopamine, acetylcholine and serotonin in mouse barrel cortex gathered by our department over the past five years, to bridge the gap between single cell, network and behavioural effects. You will use the balanced network framework to study network activity under neuromodulation. In order to do this, you will develop a balanced network description of the barrel cortex, with realistic barrel cortex properties (see https://doi.org/10.1007/s12021-022-09576-5). Next, you will incorporate the cellular effects of dopamine, acetylcholine and serotonin that we have measured over the previous years (see https://doi.org/10.1093/gigascience/giy147 and https://doi.org/10.1101/2022.01.12.476007) into the network, and investigate their effects on overall network activity and behaviour. More particularly, through simulations and analytical derivations, you will research the effects of neuromodulators on the stability of the balanced state, synchrony, regularity and chaos. You will build on the single cell data, models and analysis methods available in our group, and your results will be incorporated into our group's further research to develop and validate machine learning and efficient coding models of (somatosensory) perception. We are therefore looking for a team player who can work well with our other group members and is willing to both learn from them and share their knowledge.
Prof David Brang
We are seeking a full-time post-doctoral research fellow to study computational and neuroscientific models of perception and cognition. The research fellow will be jointly supervised by Dr. David Brang (https://sites.lsa.umich.edu/brang-lab/) and Zhongming Liu (https://libi.engin.umich.edu). The goal of this collaboration is to build computational models of cognitive and perceptual processes using data combined from electrocorticography (ECoG) and fMRI. The successful applicant will also have freedom to conduct additional research based on their interests, using a variety of methods -- ECoG, fMRI, DTI, lesion mapping, and EEG. The ideal start date is from spring to fall 2021 and the position is expected to last for at least two years, with the possibility of extension for subsequent years. We are also recruiting a Post-Doc for research on multisensory interactions (particularly how vision modulates speech perception) using Cognitive Neuroscience techniques or to help with our large-scale brain tumor collaboration with Shawn Hervey-Jumper at UCSF (https://herveyjumperlab.ucsf.edu). In this latter collaboration we collect iEEG (from ~50 patients/year) and lesion mapping data (from ~150 patients/year) in patients with a brain tumor to study sensory and cognitive functions in patients. The goals of this project are to better understand the physiology of tumors, study causal mechanisms of brain functions, and generalize iEEG/ECoG findings from epilepsy patients to a second patient population.
Prof. Isabel Beets
Postdoc position on temporal dynamics of neuropeptidergic signaling networks: https://www.kuleuven.be/personeel/jobsite/jobs/56125833?hl=en&lang=en
Dr Shuzo Sakata
A fully funded 3-year PhD studentship is available to work with Dr Shuzo Sakata at University of Strathclyde in Glasgow, UK. Our group has been investigating state-dependent information processing in the brain by combining a range of techniques, including in vivo high-density electrophysiological recording, Ca2+ imaging, optogenetics, behavioural analysis and computational approaches. In this PhD project, we will investigate whether and how manipulating brain states can modify Alzheimer’s disease pathology in mice by utilising state-of-the-art neurophotonic technologies. This project is funded by the Strathclyde Research Excellence Award scheme and will be aligned with an international consortium project, DEEPER, funded from the EU’s Horizon 2020 (https://www.deeperproject.eu/) by closely collaborating with Professor Keith Mathieson at the Institute of Photonics.
Prof. Amir Raz
We seek individuals proficient with the development and testing of novel transcranial magnetic stimulation (TMS) methods to evaluate research questions related to free will, consciousness, sense of agency, and higher brain functions.
Dr. Gabriele Scheler
We are offering a research stipend to investigate theories of memorization in neural plasticity. The focus is a critical evaluation of the role of LTP/LTD and synaptic plasticity in memory. This position is virtual and could be done part-time, or full-time for three months. The ideal candidate should have solid knowledge of neurobiology, especially plasticity mechanisms, excellent communication skills, interest and enthusiasm for next-generation neural theories, a good understanding of computation and mathematics. Programming skills are not required for this position. Detailed knowledge of one area of neural plasticity, such as synapses, intracellular pathways or genetics, is expected. Further information available on request.
Dr Sylvia Schröder
“Integration of visual and behavioural signals in the early visual system” In this project, you will discover how retinal, cortical and neuromodulatory inputs shape the responses of visual neurons in the superior colliculus. The goal of your Phd project is to understand the mechanisms of signal integration, i.e. which inputs to the superior colliculus shape its neural activity, and the advantages of this integration for visual processing. You will use two-photon imaging in awake mice to simultaneously record activity of neurons in the superior colliculus as well as of axons originating in the retina, visual cortex, or brainstem nuclei such as the dorsal raphe (serotonin). You will compare the responses of the axonal inputs to those in the neurons, and you will observe how these signals change depending on the visual input and the behaviour of the animal. In the beginning of your project, you will develop an advanced imaging technique in collaboration with our industrial partner, Scientifica. You will adapt the existing two-photon microscope to image two separate fields of view simultaneously. This technique, termed multi-region imaging, will enable you to record inputs and outputs of superior colliculus at sufficient detail, speed, and quantity.
Dr Sylvia Schröder
The successful candidate will study information processing in the early visual system of mice using two-photon imaging, electrophysiology (Neuropixels probes), and opto- and chemogenetic manipulations. The lab’s goal is to determine how behavioural and internal states like arousal are integrated with visual responses in the retina and superior colliculus. We want to discover the underlying mechanisms and the purpose of this integration in terms of visual processing and the animal’s behavioural demands. This paper describes our previous findings. Start date: January 2021 or later Contract: for 2 years initially, funding available for 5 years (through Sir Henry Dale Fellowship, Wellcome Trust) Location: campus is just outside Brighton at the coast of South East England, surrounded by South Downs National Park, 1 h from London See the job advertisement for details on how to apply: https://www.sussex.ac.uk/about/jobs/research-fellow-in-neuroscience-4726 Informal enquiries are highly encouraged and should be made to Sylvia Schröder (sylvia.schroeder@ucl.ac.uk).
Sam Neymotin
Postdoctoral scientist positions are available at the Nathan Kline Institute (NKI) for Psychiatric Research to work on computational neuroscience research funded by recently awarded NIH and DoD grants. Our NIH-funded projects investigate the brain's dynamic circuit motifs underlying internal vs. external-oriented processes in the auditory and interconnected areas, using circuit modeling of the thalamocortical system. In this project, the postdoc will build data-driven biophysical models constrained by data collected from electrophysiology labs at NKI and Columbia & The Feinstein Institutes for Medical Research, and then use the models to predict optimal neuromodulation strategies for inducing/suppressing circuit patterns, testable in vivo. Our DoD project involves developing computational models of the hippocampal and entorhinal cortex circuitry used in spatial navigation, higher level decision making circuits, and integrating the models with agents learning to solve navigation tasks using neurobiologically-inspired learning rules. This project includes mathematicians and robotics researchers at UTK and CMU.
Dr. Ziad Nahas
Dr. Ziad Nahas (Interventional Psychiatry Lab) in the University of Minnesota Department of Psychiatry and Behavioral Sciences is seeking an outstanding candidate for a postdoctoral position to conduct and analyze the effects of neuromodulation on brain activity in mood disorders. Candidates should be passionate about advancing knowledge in the area of translational research of depressive disorders and other mental health conditions with a focus on invasive and non-invasive brain stimulation treatments. The position is available June 1, 2023, and funding is available for at least two years.
Dr. Ziad Nahas
Dr. Ziad Nahas (Interventional Psychiatry Lab) in the University of Minnesota Department of Psychiatry and Behavioral Sciences is seeking an outstanding candidate for a postdoctoral position to conduct and analyze the effects of neuromodulation on brain activity in mood disorders. Candidates should be passionate about advancing knowledge in the area of translational research of depressive disorders and other mental health conditions with a focus on invasive and non-invasive brain stimulation treatments. The position is available June 1, 2023, and funding is available for at least two years.
Axel Hutt
The new research team NECTARINE at INRIA in Strasbourg / France aims to create a synergy between clinicians and mathematical researchers to develop new healthcare technologies. The team works on stochastic microscopic network models to describe macroscopic experimental data, such as behavior and/or encephalographic. They collaborate closely with clinicians and choose their research focus along the clinical applications. Major scientific objectives are stochastic multi-scale simulations and mean-field descriptions of neural activity on the macroscopic scale. Moreover, merging experimental data and numerical models by machine learning techniques is an additional objective. The team's clinical research focuses on neuromodulation of patients suffering from deficits in attention and temporal prediction. The team offers the possibility to apply for a permanent position as Chargé de Recherche (CR) or Directeur de Recherche (DR) in the research field of mathematical neuroscience with a strong focus on stochastic dynamics linking brain network modelling with experimental data.
Jie Mei
The Wiring, Neuromodeling and Brain Lab at IT:U Interdisciplinary Transformation University Austria is looking for two PhD students to work on neuromodulation-aware artificial intelligence. We are interested in (1) the role of individual neuromodulators (e.g., dopamine, serotonin, and acetylcholine) in initiating and implementing diverse biological and cognitive functions, (2) how competition and cooperation among neuromodulators enrich single neuromodulator computations, and (3) how multi-neuromodulator dynamics can be translated into learning rules for more flexible, robust, and adaptive learning in artificial neural networks (ANNs). Start date: Jan-Mar 2025. Apply by Nov 30, 2024: https://it-u.at/en/research/research-groups/computational-neuroscience/ For more information, please visit: https://majorjiemei.wixsite.com/wnblab If you have any questions, please contact Dr. Jie Mei (jie.mei@it-u.at).
Jie Mei
The Wiring, Neuromodeling and Brain Lab at IT:U Interdisciplinary Transformation University Austria is offering 2 PhD positions in neuromodulation-aware artificial intelligence. We are interested in (1) the role of individual neuromodulators (e.g., dopamine, serotonin, and acetylcholine) in initiating and implementing diverse biological and cognitive functions, (2) how competition and cooperation among neuromodulators enrich single neuromodulator computations, and (3) how multi-neuromodulator dynamics can be translated into learning rules for more flexible, robust, and adaptive learning in artificial neural networks.
Assistant Professor Yao Chen
Research Assistant - Neuroscience Dr. Yao Chen’s interdisciplinary lab in the Department of Neuroscience at Washington University School of Medicine is seeking a highly motivated, hardworking, and intellectually curious individual for a full-time Research Assistant position. Our lab aims to understand how biochemical signaling dynamics contribute to neuromodulator actions, learning, and mechanisms of sleep functions through basic research of the mouse brain. We are looking for a fearless, proactive individual who is receptive to feedback and eager to grow scientifically, technically, and personally. The successful candidate may have the opportunity to lead projects with guidance from the Principal Investigator (PI) and in collaboration with other lab members. The applicant will receive training and support on research design, experimental execution, and data interpretation. The PI is committed to nurturing a creative, collaborative, and supportive lab culture. Washington University neuroscience is ranked among the top 10 in the world. The School of Medicine is ranked among the top 5 medical schools in the United States.
Dr. Fleur Zeldenrust
For the Vidi project ‘Top-down neuromodulation and bottom-up network computation,’ we seek a postdoc to study neuromodulators in efficient spike-coding networks. Using our lab’s data on dopamine, acetylcholine, and serotonin from the mouse barrel cortex, you’ll derive models connecting single cells, networks, and behavior. The aim of this project is to explain the effects of neuromodulation on task performance in biologically realistic spiking recurrent neural networks (SRNNs). You will use the efficient spike coding framework, in which a network is not trained by a learning paradigm but deduced using mathematically rigorous rules that enforce efficient coding (i.e. maximally informative spikes). You will study how the network’s structural properties such as neural heterogeneity influence decoding performance and efficiency. You will incorporate realistic network properties of the (barrel) cortex based on our lab’s measurements and incorporate the cellular effects of dopamine, acetylcholine and serotonin we have measured over the past years into the network, to investigate their effects on representations, network activity measures such as dimensionality, and decoding performance. You will build on the single cell data, network models and analysis methods available in our group, and your results will be incorporated into our group’s further research to develop and validate efficient coding models of (somatosensory) perception. Therefore, we are looking for a team player who is willing to learn from the other group members and to share their knowledge with them.
Dr Margarita Zachariou
We are looking for a Post-Doctoral Fellow and/or a Laboratory Scientific Officer(research assistant) to join the Bioinformatics Department of the Cyprus Institute of Neurology and Genetics. The team focuses on computational neuroscience, particularly on (1) building biophysical models of neurons and neuronal networks to study neurological diseases and (2) developing state-of-the-art analysis pipelines for neural data across scales, focusing on disease-specific patterns and integrating diverse data modalities. The successful candidate(s) will be working on multiscale models of magnetoelectric and ultrasonic effects on neuronal dynamics as part of the EU-Horizon funded META-BRAIN (https://meta-brain.eu).
Neural circuits underlying sleep structure and functions
Sleep is an active state critical for processing emotional memories encoded during waking in both humans and animals. There is a remarkable overlap between the brain structures and circuits active during sleep, particularly rapid eye-movement (REM) sleep, and the those encoding emotions. Accordingly, disruptions in sleep quality or quantity, including REM sleep, are often associated with, and precede the onset of, nearly all affective psychiatric and mood disorders. In this context, a major biomedical challenge is to better understand the underlying mechanisms of the relationship between (REM) sleep and emotion encoding to improve treatments for mental health. This lecture will summarize our investigation of the cellular and circuit mechanisms underlying sleep architecture, sleep oscillations, and local brain dynamics across sleep-wake states using electrophysiological recordings combined with single-cell calcium imaging or optogenetics. The presentation will detail the discovery of a 'somato-dendritic decoupling'in prefrontal cortex pyramidal neurons underlying REM sleep-dependent stabilization of optimal emotional memory traces. This decoupling reflects a tonic inhibition at the somas of pyramidal cells, occurring simultaneously with a selective disinhibition of their dendritic arbors selectively during REM sleep. Recent findings on REM sleep-dependent subcortical inputs and neuromodulation of this decoupling will be discussed in the context of synaptic plasticity and the optimization of emotional responses in the maintenance of mental health.
Homeostatic Neural Responses to Photic Stimulation
This talk presents findings from open and closed-loop neural stimulation experiments using EEG. Fixed-frequency (10 Hz) stimulation revealed cross-cortical alpha power suppression post-stimulation, modulated by the difference between the individual's alpha frequency and the stimulation frequency. Closed-loop stimulation demonstrated phase-dependent effects: trough stimulation enhanced lower alpha activity, while peak stimulation suppressed high alpha to beta activity. These findings provide evidence for homeostatic mechanisms in the brain's response to photic stimulation, with implications for neuromodulation applications.
Charting the fetal development of neural complexity
Evolution of convulsive therapy from electroconvulsive therapy to Magnetic Seizure Therapy; Interventional Neuropsychiatry
In April, we will host Nolan Williams and Mustafa Husain. Be prepared to embark on a journey from early brain stimulation with ECT to state-of-the art TMS protocols and magnetic seizure therapy! The talks will be held on Thursday, April 25th at noon ET / 6PM CET. Nolan Williams, MD, is an associate professor of Psychiatry and Behavioral Science at Stanford University. He developed the SAINT protocol, which is the first FDA-cleared non-invasive, rapid-acting neuromodulation treatment for treatment-resistant depression. Mustafa Husain, MD, is an adjunct professor of Psychiatry and Behavioral Sciences at Duke University and a professor of Psychiatry and Neurology at UT Southwestern Medical Center, Dallas. He will tell us about “Evolution of convulsive therapy from electroconvulsive therapy to Magnetic Seizure Therapy”. As always, we will also get a glimpse at the “Person behind the science”. Please register va talks.stimulatingbrains.org to receive the (free) Zoom link, subscribe to our newsletter, or follow us on Twitter/X for further updates!
Currents of Hope: how noninvasive brain stimulation is reshaping modern psychiatric care; Adapting to diversity: Integrating variability in brain structure and function into personalized / closed-loop non-invasive brain stimulation for substance use disorders
In March we will focus on TMS and host Ghazaleh Soleimani and Colleen Hanlon. The talks will talk place on Thursday, March 28th at noon ET – please be aware that this means 5PM CET since Boston already switched to summer time! Ghazaleh Soleimani, PhD, is a postdoctoral fellow in Dr Hamed Ekhtiari’s lab at the University of Minnesota. She is also the executive director of the International Network of tES/TMS for Addiction Medicine (INTAM). She will discuss “Adapting to diversity: Integrating variability in brain structure and function into personalized / closed-loop non-invasive brain stimulation for substance use disorders”. Colleen Hanlon, PhD, currently serves as a Vice President of Medical Affairs for BrainsWay, a company specializing in medical devices for mental health, including TMS. Colleen previously worked at the Medical University of South Carolina and Wake Forest School of Medicine. She received the International Brain Stimulation Early Career Award in 2023. She will discuss “Currents of Hope: how noninvasive brain stimulation is reshaping modern psychiatric care”. As always, we will also get a glimpse at the “Person behind the science”. Please register va talks.stimulatingbrains.org to receive the (free) Zoom link, subscribe to our newsletter, or follow us on Twitter/X for further updates!
Novel approaches to non-invasive neuromodulation for neuropsychiatric disorders; Effects of deep brain stimulation on brain function in obsessive-compulsive disorder
On Thursday, February 29th, we will host Damiaan Denys and Andrada Neacsiu. The talks will be followed by a shared discussion. You can register via talks.stimulatingbrains.org to receive the (free) Zoom link!
Closed-loop deep brain stimulation as a neuroprosthetic of dopaminergic circuits – Current evidence and future opportunities; Spatial filtering to enhance signal processing in invasive neurophysiology
On Thursday February 15th, we will host Victoria Peterson and Julian Neumann. Victoria will tell us about “Spatial filtering to enhance signal processing in invasive neurophysiology”. Besides his scientific presentation on “Closed-loop deep brain stimulation as a neuroprosthetic of dopaminergic circuits – Current evidence and future opportunities”, Julian will give us a glimpse at the person behind the science. The talks will be followed by a shared discussion. Note: The talks will exceptionally be held at 10 ET / 4PM CET. You can register via talks.stimulatingbrains.org to receive the (free) Zoom link!
Neuromodulation of striatal D1 cells shapes BOLD fluctuations in anatomically connected thalamic and cortical regions
Understanding how macroscale brain dynamics are shaped by microscale mechanisms is crucial in neuroscience. We investigate this relationship in animal models by directly manipulating cellular properties and measuring whole-brain responses using resting-state fMRI. Specifically, we explore the impact of chemogenetically neuromodulating D1 medium spiny neurons in the dorsomedial caudate putamen (CPdm) on BOLD dynamics within a striato-thalamo-cortical circuit in mice. Our findings indicate that CPdm neuromodulation alters BOLD dynamics in thalamic subregions projecting to the dorsomedial striatum, influencing both local and inter-regional connectivity in cortical areas. This study contributes to understanding structure–function relationships in shaping inter-regional communication between subcortical and cortical levels.
Imaging the subcortex; Microstructural and connectivity correlates of outcome variability in functional neurosurgery for movement disorders
We are very much looking forward to host Francisca Ferreira and Birte Forstmann on December 14th, 2023, at noon ET / 6PM CET. Francisca Ferreira is a PhD student and Neurosurgery trainee at the University College of London Queen Square Institute of Neurology and a Royal College of Surgeons “Emerging Leaders” program laureate. Her presentation title will be: “Microstructural and connectivity correlates of outcome variability in functional neurosurgery for movement disorders”. Birte Forstmann, PhD, is the Director of the Amsterdam Brain and Cognition Center, a Professor of Cognitive Neuroscience at the University of Amsterdam, and a Professor by Special Appointment of Neuroscientific Testing of Psychological Models at the University of Leiden. Besides her scientific presentation (“Imaging the human subcortex”), she will give us a glimpse at the “Person behind the science”. You can register via talks.stimulatingbrains.org to receive the (free) Zoom link!
Neuromodulation of subjective experience
Many psychoactive substances are used with the aim of altering experience, e.g. as analgesics, antidepressants or antipsychotics. These drugs act on specific receptor systems in the brain, including the opioid, serotonergic and dopaminergic systems. In this talk, I will summarise human drug studies targeting opioid receptors and their role for human experience, with focus on the experience of pain, stress, mood, and social connection. Opioids are only indicated for analgesia, due to their potential to cause addiction. When these regulations occurred, other known effects were relegated to side effects. This may be the cause of the prevalent myth that opioids are the most potent painkillers, despite evidence from head-to-head trials, Cochrane reviews and network meta-analyses that opioids are not superior to non-opioid analgesics in the treatment of acute or chronic non-cancer pain. However, due to the variability and diversity of opioid effects across contexts and experiences, some people under some circumstances may indeed benefit from prolonged treatment. I will present data on individual differences in opioid effects due to participant sex and stress induction. Understanding the effects of these commonly used medications on other aspects of the human experience is important to ensure correct use and to prevent unnecessary pain and addiction risk.
From primate anatomy to human neuroimaging: insights into the circuits underlying psychiatric disease and neuromodulation; Large-scale imaging of neural circuits: towards a microscopic human connectome
On Thursday, October 26th, we will host Anastasia Yendiki and Suzanne Haber. Anastasia Yendiki, PhD, is an Associate Professor in Radiology at the Harvard Medical School and an Associate Investigator at the Massachusetts General Hospital and Athinoula A. Martinos Center. Suzanne Haber, PhD, is a Professor at the University of Rochester and runs a lab at McLean hospital at Harvard Medical School in Boston. She has received numerous awards for her work on neuroanatomy. Beside her scientific presentation, she will give us a glimpse at the “Person behind the science”. The talks will be followed by a shared discussion. You can register via talks.stimulatingbrains.org to receive the (free) Zoom link!
Quality of life after DBS; Non-motor effects of DBS and quality of life
It’s our pleasure to announce that we will host Haidar Dafsari and Günther Deuschl on September 28th at noon ET / 6PM CET. Haidar Dafsari, MD, is a researcher and lecturer at the University Hospital Cologne. Günther Deuschl, MD, PhD, is a professor at Kiel University. He was president of the International Movement Disorders Society (MDS) from 2011-2013, Editor in Chief of the journal Movement Disorders and has been awarded numerous high-class awards. Beside his scientific presentation, he will give us a glimpse at the “Person behind the science”.The talks will be followed by a shared discussion. You can register via talks.stimulatingbrains.org to receive the (free) Zoom link!
Adaptive deep brain stimulation to treat gait disorders in Parkinson's disease; Personalized chronic adaptive deep brain stimulation outperforms conventional stimulation in Parkinson's disease
On Friday, August 31st we will host Stephanie Cernera & Doris Wang! Stephanie Cernera, PhD, is a postdoctoral research fellow in the Starr lab at University of California San Francisco. She will tell us about “Personalized chronic adaptive deep brain stimulation outperforms conventional stimulation in Parkinson’s Disease”. Doris Wang, MD, PhD, is a neurosurgeon and assistant professor at the University of California San Francisco. Apart from her scientific presentation about “Adaptive Deep Brain Stimulation to Treat Gait Disorders in Parkinson’s Disease”, she will give us a glimpse at the “Person behind the science”. The talks will be followed by a shared discussion. You can register via talks.stimulatingbrains.org to receive the (free) Zoom link!
Auditory input to the basal ganglia; Deep brain stimulation and action-stopping: A cognitive neuroscience perspective on the contributions of fronto-basal ganglia circuits to inhibitory control
On Thursday, May 25th we will host Darcy Diesburg and Mark Richardson. Darcy Diesburg, PhD, is a post-doctoral research fellow at Brown University. She will tell us about “Deep brain stimulation and action-stopping: A cognitive neuroscience perspective on the contributions of fronto-basal ganglia circuits to inhibitory control”. Mark Richardson, MD, PhD, is the Director of Functional Neurosurgery at the Massachusetts General Hospital, Charles Pappas Associate Professor of Neurosciences at Harvard Medical School and Visiting Associate Professor of Brain and Cognitive Sciences at MIT. Beside his scientific presentation on “Auditory input to the basal ganglia”, he will give us a glimpse at the “Person behind the science”. The talks will be followed by a shared discussion. You can register via talks.stimulatingbrains.org to receive the (free) Zoom link!
My evolution in invasive human neurophysiology: From basal ganglia single units to chronic electrocorticography; Therapies orchestrated by patients' own rhythms
On Thursday, April 27th, we will host Hayriye Cagnan and Philip A. Starr. Hayriye Cagnan, PhD, is an associate professor at the MRC Brain Network Dynamics Unit and University of Oxford. She will tell us about “Therapies orchestrated by patients’ own rhythms”. Philip A. Starr, MD, PhD, is a neurosurgeon and professor of Neurological Surgery at the University of California San Francisco. Besides his scientific presentation on “My evolution in invasive human neurophysiology: from basal ganglia single units to chronic electrocorticography”, he will give us a glimpse at the person behind the science. The talks will be followed by a shared discussion. You can register via talks.stimulatingbrains.org to receive the (free) Zoom link!
Causal Symptom Network Mapping Based on Lesions and Brain Stimulation; Converging Evidence about a Depression Circuit Using Causal Sources of Information
It’s our pleasure to announce that we will host Shan Siddiqi and Michael D. Fox on Thursday, March 30th at noon ET / 6PM CET. Shan Siddiqi, MD, is an Assistant Professor of Psychiatry at Harvard Medical School and the director of Psychiatric Neuromodulation Research at the Brigham and Women’s Hospital. Michael D. Fox, MD, PhD, is an Associate Professor of Neurology at Harvard Medical School and the founding director of the Center for Brain Circuit Therapeutics at the Brigham and Women’s Hospital. The talks will be followed by a shared discussion. You can register via talks.stimulatingbrains.org to receive the (free) Zoom link!
Integrative Neuromodulation: from biomarker identification to optimizing neuromodulation
Why do we make decisions impulsively blinded in an emotionally rash moment? Or caught in the same repetitive suboptimal loop, avoiding fears or rushing headlong towards illusory rewards? These cognitive constructs underlying self-control and compulsive behaviours and their influence by emotion or incentives are relevant dimensionally across healthy individuals and hijacked across disorders of addiction, compulsivity and mood. My lab focuses on identifying theory-driven modifiable biomarkers focusing on these cognitive constructs with the ultimate goal to optimize and develop novel means of neuromodulation. Here I will provide a few examples of my group’s recent work to illustrate this approach. I describe a series of recent studies on intracranial physiology and acute stimulation focusing on risk taking and emotional processing. This talk highlights the subthalamic nucleus, a common target for deep brain stimulation for Parkinson’s disease and obsessive-compulsive disorder. I further describe recent translational work in non-invasive neuromodulation. Together these examples illustrate the approach of the lab highlighting modifiable biomarkers and optimizing neuromodulation.
25 years of DBS beyond movement disorders: what challenges are we facing?; Directional DBS targeting of different nuclei in the thalamus for the treatment of pain
On Thursday, 23rd of February, we will host Veerle Visser-Vandewalle and Marie Krüger. Marie Krüger, MD, is is currently leading the stereotactic surgery unit in St. Gallen but is on her move to join the team at UCL / Queensquare London. She will discuss “Directional DBS targeting of different nuclei in the thalamus for the treatment of pain”. Veerle Visser-Vandewalle, MD, PhD, is the Head of the Department of Stereotactic and Functional Neurosurgery at University Hospital of Cologne. Beside his scientific presentation on “25 years of DBS beyond movement disorders: what challenges are we facing?”, she will also give us a glimpse at the “Person behind the science”. The talks will be followed by a shared discussion. You can register via talks.stimulatingbrains.org to receive the (free) Zoom link!
Beta oscillations in the basal ganglia: Past, Present and Future; Oscillatory signatures of motor symptoms across movement disorders
On Wednesday, January 25th, at noon ET / 6PM CET, we will host Roxanne Lofredi and Hagai Bergman. Roxanne Lofredi, MD, is a research fellow in the Movement Disorders and Neuromodulation Unit at Charité Universitätsmedizin Berlin. Hagai Bergman, MD, PhD, is a Professor of Physiology in the Edmond and Lily Safra Center for Brain Research and Faculty of Medicine at the Hebrew University of Jerusalem, and is Simone and Bernard Guttman Chair in Brain Research. Beside his scientific presentation on “Beta oscillations in the basal ganglia: Past, Present and Future”, he will also give us a glimpse at the “Person behind the science”. The talks will be followed by a shared discussion. You can register via talks.stimulatingbrains.org to receive the (free) Zoom link!
Maths, AI and Neuroscience Meeting Stockholm
To understand brain function and develop artificial general intelligence it has become abundantly clear that there should be a close interaction among Neuroscience, machine learning and mathematics. There is a general hope that understanding the brain function will provide us with more powerful machine learning algorithms. On the other hand advances in machine learning are now providing the much needed tools to not only analyse brain activity data but also to design better experiments to expose brain function. Both neuroscience and machine learning explicitly or implicitly deal with high dimensional data and systems. Mathematics can provide powerful new tools to understand and quantify the dynamics of biological and artificial systems as they generate behavior that may be perceived as intelligent.
Bridging the gap from research to clinical decision making in epilepsy neuromodulation; How to become an integral part of the functional neurosurgery team as a radiologist
On Wednesday, November 30th, at noon ET / 6PM CET, we will host Alexandre Boutet and Erik H. Middlebrooks. Alexandre Boutet, MD, PhD, is a neuroradiology fellow at the University of Toronto, and will tell us about “How to become an integral part of the functional neurosurgery team as a radiologist”. Erik H. Middlebrooks, MD, is a Professor and Consultant of Neuroradiology and Neurosurgery and the Neuroradiology Program Director at Mayo Clinic. Beside his scientific presentation about “Bridging the Gap from Research to Clinical Decision Making in Epilepsy Neuromodulation”, he will also give us a glimpse at the “Person behind the science”. The talks will be followed by a shared discussion. You can register via talks.stimulatingbrains.org to receive the (free) Zoom link!
Neurosurgery for Mental Disorders: Challenging Mindsets; Combining Neuroimaging and Neurophysiology in Parkinson’s Disease
On Wednesday, October 26th, at noon ET / 6PM CET, we will host Kara Johnson, PhD, and Ludvic Zrinzo, MD PhD, for the inaugural session of our newly conceived talk series format entitled "Stimulating Brains". Kara A. Johnson, a postdoctoral fellow in Dr. Coralie de Hemptinne’s lab at the University of Florida, will present her work on “Combining imaging and neurophysiology in Parkinson’s disease”. Ludvic Zrinzo, Professor of functional neurosurgery and head of the University College London functional neurosurgery unit, will give us a glimpse at the “Person behind the science”, and give a talk on “Neurosurgery for mental disorders: challenging mindsets”. The talks will be followed by a shared discussion. You can register via talks.stimulatingbrains.org to receive the (free) Zoom link!
Brain and behavioural impacts of early life adversity
Abuse, neglect, and other forms of uncontrollable stress during childhood and early adolescence can lead to adverse outcomes later in life, including especially perturbations in the regulation of mood and emotional states, and specifically anxiety disorders and depression. However, stress experiences vary from one individual to the next, meaning that causal relationships and mechanistic accounts are often difficult to establish in humans. This interdisciplinary talk considers the value of research in experimental animals where stressor experiences can be tightly controlled and detailed investigations of molecular, cellular, and circuit-level mechanisms can be carried out. The talk will focus on the widely used repeated maternal separation procedure in rats where rat offspring are repeatedly separated from maternal care during early postnatal life. This early life stress has remarkably persistent effects on behaviour with a general recognition that maternally-deprived animals are susceptible to depressive-like phenotypes. The validity of this conclusion will be critically appraised with convergent insights from a recent longitudinal study in maternally separated rats involving translational brain imaging, transcriptomics, and behavioural assessment.
Neuromodulation of sleep integrity
The arousal construct underlies a spectrum of behaviors that include sleep, exploration, feeding, sexual activity and adaptive stress. Pathological arousal conditions include stress, anxiety disorders, and addiction. The dynamics between arousal state transitions are modulated by norepinephrine neurons in the locus coeruleus, histaminergic neurons in the hypothalamus, dopaminergic neurons in the mesencephalon and cholinergic neurons in the basal forebrain. The hypocretin/orexin system in the lateral hypothalamus I will also present a new mechanism underlying sleep fragmentation during aging. Hcrt neurons are hyperexcitable in aged mice. We identify a potassium conductance known as the M-current, as a critical player in maintaining excitability of Hcrt neurons. Genetic disruption of KCNQ channels in Hcrt neurons of young animals results in sleep fragmentation. In contrast, treatment of aged animals with a KCNQ channel opener restores sleep/wake architecture. These data point to multiple circuits modulating sleep integrity across lifespan.
Neuromodulation of inference and control in the cortical circuits
Neural circuits for novel choices and for choice speed and accuracy changes in macaques
While most experimental tasks aim at isolating simple cognitive processes to study their neural bases, naturalistic behaviour is often complex and multidimensional. I will present two studies revealing previously uncharacterised neural circuits for decision-making in macaques. This was possible thanks to innovative experimental tasks eliciting sophisticated behaviour, bridging the human and non-human primate research traditions. Firstly, I will describe a specialised medial frontal circuit for novel choice in macaques. Traditionally, monkeys receive extensive training before neural data can be acquired, while a hallmark of human cognition is the ability to act in novel situations. I will show how this medial frontal circuit can combine the values of multiple attributes for each available novel item on-the-fly to enable efficient novel choices. This integration process is associated with a hexagonal symmetry pattern in the BOLD response, consistent with a grid-like representation of the space of all available options. We prove the causal role played by this circuit by showing that focussed transcranial ultrasound neuromodulation impairs optimal choice based on attribute integration and forces the subjects to default to a simpler heuristic decision strategy. Secondly, I will present an ongoing project addressing the neural mechanisms driving behaviour shifts during an evidence accumulation task that requires subjects to trade speed for accuracy. While perceptual decision-making in general has been thoroughly studied, both cognitively and neurally, the reasons why speed and/or accuracy are adjusted, and the associated neural mechanisms, have received little attention. We describe two orthogonal dimensions in which behaviour can vary (traditional speed-accuracy trade-off and efficiency) and we uncover independent neural circuits concerned with changes in strategy and fluctuations in the engagement level. The former involves the frontopolar cortex, while the latter is associated with the insula and a network of subcortical structures including the habenula.
Separable pupillary signatures of perception and action during perceptual multistability
The pupil provides a rich, non-invasive measure of the neural bases of perception and cognition, and has been of particular value in uncovering the role of arousal-linked neuromodulation, which alters cortical processing as well as pupil size. But pupil size is subject to a multitude of influences, which complicates unique interpretation. We measured pupils of observers experiencing perceptual multistability -- an ever-changing subjective percept in the face of unchanging but inconclusive sensory input. In separate conditions the endogenously generated perceptual changes were either task-relevant or not, allowing a separation between perception-related and task-related pupil signals. Perceptual changes were marked by a complex pupil response that could be decomposed into two components: a dilation tied to task execution and plausibly indicative of an arousal-linked noradrenaline surge, and an overlapping constriction tied to the perceptual transient and plausibly a marker of altered visual cortical representation. Constriction, but not dilation, amplitude systematically depended on the time interval between perceptual changes, possibly providing an overt index of neural adaptation. These results show that the pupil provides a simultaneous reading on interacting but dissociable neural processes during perceptual multistability, and suggest that arousal-linked neuromodulation shapes action but not perception in these circumstances. This presentation covers work that was published in e-life
Dynamic Neuromodulation
Context-Dependent Relationships between Locus Coeruleus Firing Patterns and Coordinated Neural Activity in the Anterior Cingulate Cortex
Ascending neuromodulatory projections from the locus coeruleus (LC) affect cortical neural networks via the release of norepinephrine (NE). However, the exact nature of these neuromodulatory effects on neural activity patterns in vivo is not well understood. Here we show that in awake monkeys, LC activation is associated with changes in coordinated activity patterns in the anterior cingulate cortex (ACC). These relationships, which are largely independent of changes in firing rates of individual ACC neurons, depend on the type of LC activation: ACC pairwise correlations tend to be reduced when tonic (baseline) LC activity increases but are enhanced when external events drive phasic LC responses. Both relationships covary with pupil changes that reflect LC activation and arousal. These results suggest that modulations of information processing that reflect changes in coordinated activity patterns in cortical networks can result partly from ongoing, context-dependent, arousal-related changes in activation of the LC-NE system.
Analyzing Retinal Disease Using Electron Microscopic Connectomics
John DowlingJohn E. Dowling received his AB and PhD from Harvard University. He taught in the Biology Department at Harvard from 1961 to 1964, first as an Instructor, then as assistant professor. In 1964 he moved to Johns Hopkins University, where he held an appointment as associate professor of Ophthalmology and Biophysics. He returned to Harvard as professor of Biology in 1971, was the Maria Moors Cabot Professor of Natural Sciences from 1971-2001, Harvard College professor from 1999-2004 and is presently the Gordon and Llura Gund Professor of Neurosciences. Dowling was chairman of the Biology Department at Harvard from 1975 to 1978 and served as associate dean of the faculty of Arts and Sciences from 1980 to 1984. He was Master of Leverett House at Harvard from 1981-1998 and currently serves as president of the Corporation of The Marine Biological Laboratory in Woods Hole. He is a Fellow of the American Academy of Arts and Sciences, a member of the National Academy of Sciences and a member of the American Philosophical Society. Awards that Dowling received include the Friedenwald Medal from the Association of Research in Ophthalmology and Vision in 1970, the Annual Award of the New England Ophthalmological Society in 1979, the Retinal Research Foundation Award for Retinal Research in 1981, an Alcon Vision Research Recognition Award in 1986, a National Eye Institute's MERIT award in 1987, the Von Sallman Prize in 1992, The Helen Keller Prize for Vision Research in 2000 and the Llura Ligget Gund Award for Lifetime Achievement and Recognition of Contribution to the Foundation Fighting Blindness in 2001. He was granted an honorary MD degree by the University of Lund (Sweden) in 1982 and an honorary Doctor of Laws degree from Dalhousie University (Canada) in 2012. Dowling's research interests have focused on the vertebrate retina as a model piece of the brain. He and his collaborators have long been interested in the functional organization of the retina, studying its synaptic organization, the electrical responses of the retinal neurons, and the mechanisms underlying neurotransmission and neuromodulation in the retina. Dowling became interested in zebrafish as a system in which one could explore the development and genetics of the vertebrate retina about 20 years ago. Part of his research team has focused on retinal development in zebrafish and the role of retinoic acid in early eye and photoreceptor development. A second group has developed behavioral tests to isolate mutations, both recessive and dominant, specific to the visual system.
Electrophysiologic Monitoring and Modulation of Enteric Nervous System
We will highlight recent technological and methodological advances in deploying miniaturized technologies that can monitor the spatial electrophysiologic patterns of the visceral nervous system. As an example, we will discuss recent developments of thin, stretchable, wireless biosensor patches that can be embedded within routinely used medical adhesives for recording electrophysiologic patterns of the GI tract. We will also showcase recent developments in array signal processing that enable non-invasive tracking, and source localization, of the slow wave patterns associated with the GI tract. We will illustrate how such systems can also be used in tandem with novel miniaturized pacing devices to can enable closed-loop neuromodulation of the enteric nervous system. We will conclude with a summary of the knowns and unknowns in how multi-organ physiology research, technology miniaturization, and data science may create unique opportunities for the intersection of electrical engineering and neuroscience.
Acetylcholine modulation of short-term plasticity is critical to reliable long-term plasticity in hippocampal synapses
CA3-CA1 synapses in the hippocampus are the initial locus of episodic memory. The action of acetylcholine alters cellular excitability, modifies neuronal networks, and triggers secondary signaling that directly affects long-term plasticity (LTP) (the cellular underpinning of memory). It is therefore considered a critical regulator of learning and memory in the brain. Its action via M4 metabotropic receptors in the presynaptic terminal of the CA3 neurons and M1 metabotropic receptors in the postsynaptic spines of CA1 neurons produce rich dynamics across multiple timescales. We developed a model to describe the activation of postsynaptic M1 receptors that leads to IP3 production from membrane PIP2 molecules. The binding of IP3 to IP3 receptors in the endoplasmic reticulum (ER) ultimately causes calcium release. This calcium release from the ER activates potassium channels like the calcium-activated SK channels and alters different aspects of synaptic signaling. In an independent signaling cascade, M1 receptors also directly suppress SK channels and the voltage-activated KCNQ2/3 channels, enhancing post-synaptic excitability. In the CA3 presynaptic terminal, we model the reduction of the voltage sensitivity of voltage-gated calcium channels (VGCCs) and the resulting suppression of neurotransmitter release by the action of the M4 receptors. Our results show that the reduced initial release probability because of acetylcholine alters short-term plasticity (STP) dynamics. We characterize the dichotomy of suppressing neurotransmitter release from CA3 neurons and the enhanced excitability of the postsynaptic CA1 spine. Mechanisms underlying STP operate over a few seconds, while those responsible for LTP last for hours, and both forms of plasticity have been linked with very distinct functions in the brain. We show that the concurrent suppression of neurotransmitter release and increased sensitivity conserves neurotransmitter vesicles and enhances the reliability in plasticity. Our work establishes a relationship between STP and LTP coordinated by neuromodulation with acetylcholine.
How inclusive and diverse is non-invasive brain stimulation in the treatment of psychiatric disorders?
How inclusive and diverse is non-invasive brain stimulation in the treatment of psychiatric disorders?Indira Tendolkar, Donders Institute for Brain, Cognition and Behavior, Department of Psychiatry. Mental illness is associated with a huge socioeconomic burden worldwide, with annual costs only in the Netherlands of €22 billion. Over two decades of cognitive and affective neuroscience research with modern tools of neuroimaging and neurophysiology in humans have given us a wealth of information about neural circuits underlying the main symptom domains of psychiatric disorders and their remediation. Neuromodulation entails the alteration of these neural circuits through invasive (e.g., DBS) or non-invasive (e.g., TMS) techniques with the aim of improving symptoms and/or functions and enhancing neuroplasticity. In my talk, I will focus on neuromodulation studies using repetitive transcranial magnetic stimulation (rTMS) as a relatively safe, noninvasive method, which can be performed simultaneously with neurocognitive interventions. Using the examples of two chronifying mental illnesses, namely obsessive compulsive disorders and major depressive disorder (MDD), I will review the concept of "state dependent" effects of rTMS and highlight how simultaneous or sequential cognitive interventions could help optimize rTMS therapy by providing further control of ongoing neural activity in targeted neural networks. Hardly any attention has been paid to diversity aspects in the studies. By including studies from low- and middle income countries, I will discuss the potential of non-invasive brain stimulation from a transcultural perspective.
An in-silico framework to study the cholinergic modulation of the neocortex
Neuromodulators control information processing in cortical microcircuits by regulating the cellular and synaptic physiology of neurons. Computational models and detailed simulations of neocortical microcircuitry offer a unifying framework to analyze the role of neuromodulators on network activity. In the present study, to get a deeper insight in the organization of the cortical neuropil for modeling purposes, we quantify the fiber length per cortical volume and the density of varicosities for catecholaminergic, serotonergic and cholinergic systems using immunocytochemical staining and stereological techniques. The data obtained are integrated into a biologically detailed digital reconstruction of the rodent neocortex (Markram et al, 2015) in order to model the influence of modulatory systems on the activity of the somatosensory cortex neocortical column. Simulations of ascending modulation of network activity in our model predict the effects of increasing levels of neuromodulators on diverse neuron types and synapses and reveal a spectrum of activity states. Low levels of neuromodulation drive microcircuit activity into slow oscillations and network synchrony, whereas high neuromodulator concentrations govern fast oscillations and network asynchrony. The models and simulations thus provide a unifying in silico framework to study the role of neuromodulators in reconfiguring network activity.
Effects of Vagus Nerve Stimulation on Arousal State and Cortical Excitation
The vagus nerve is a major pathway by which the brain and the body communicate. Electrical stimulation of the vagus nerve (VNS) is widely used as a therapeutic intervention for epilepsy and there is compelling evidence that it can enhance recovery following stroke. Our work demonstrates that VNS exerts a robust excitatory effect on the brain. First, we establish that VNS triggers an increase in arousal state as measured by behavioral state change. This behavioral state change is linked to an increase in excitatory activity within the cortex. We also show that cholinergic and noradrenergic neuromodulatory pathways are activated by VNS, providing a potential mechanism by which VNS may trigger cortical activation. Importantly, the effect of VNS on neuromodulation and cortical excitation persists in anesthetized mice, demonstrating that VNS-induced cortical activation cannot be fully explained by associated behavioral changes.
State-dependent cortical circuits
Spontaneous and sensory-evoked cortical activity is highly state-dependent, promoting the functional flexibility of cortical circuits underlying perception and cognition. Using neural recordings in combination with behavioral state monitoring, we find that arousal and motor activity have complementary roles in regulating local cortical operations, providing dynamic control of sensory encoding. These changes in encoding are linked to altered performance on perceptual tasks. Neuromodulators, such as acetylcholine, may regulate this state-dependent flexibility of cortical network function. We therefore recently developed an approach for dual mesoscopic imaging of acetylcholine release and neural activity across the entire cortical mantle in behaving mice. We find spatiotemporally heterogeneous patterns of cholinergic signaling across the cortex. Transitions between distinct behavioral states reorganize the structure of large-scale cortico-cortical networks and differentially regulate the relationship between cholinergic signals and neural activity. Together, our findings suggest dynamic state-dependent regulation of cortical network operations at the levels of both local and large-scale circuits. Zoom Meeting ID: 964 8138 3003 Contact host if you cannot connect.
The retrotrapezoid nucleus: an integrative and interoceptive hub in neural control of breathing
In this presentation, we will discuss the cellular and molecular properties of the retrotrapezoid nucleus (RTN), an integrative and interoceptive control node for the respiratory motor system. We will present the molecular profiling that has allowed definitive identification of a cluster of tonically active neurons that provide a requisite drive to the respiratory central pattern generator (CPG) and other pre-motor neurons. We will discuss the ionic basis for steady pacemaker-like firing, including by a large subthreshold oscillation; and for neuromodulatory influences on RTN activity, including by arousal state-dependent neurotransmitters and CO2/H+. The CO2/H+-dependent modulation of RTN excitability represents the sensory component of a homeostatic system by which the brain regulates breathing to maintain blood gases and tissue pH; it relies on two intrinsic molecular proton detectors, both a proton-activated G protein-coupled receptor (GPR4) and a proton-inhibited background K+ channel (TASK-2). We will also discuss downstream neurotransmitter signaling to the respiratory CPG, focusing especially on a newly-identified peptidergic modulation of the preBötzinger complex that becomes activated following birth and the initiation of air breathing. Finally, we will suggest how the cellular and molecular properties of RTN neurons identified in rodent models may contribute to understanding human respiratory disorders, such as congenital central hypoventilation syndrome (CCHS) and sudden infant death syndrome (SIDS).
Arousal modulates retinal output
Neural responses in the visual system are usually not purely visual but depend on behavioural and internal states such as arousal. This dependence is seen both in primary visual cortex (V1) and in subcortical brain structures receiving direct retinal input. In this talk, I will show that modulation by behavioural state arises as early as in the output of the retina.To measure retinal activity in the awake, intact brain, we imaged the synaptic boutons of retinal axons in the superficial superior colliculus (sSC) of mice. The activity of about half of the boutons depended not only on vision but also on running speed and pupil size, regardless of retinal illumination. Arousal typically reduced the boutons’ visual responses to preferred direction and their selectivity for direction and orientation.Arousal may affect activity in retinal boutons by presynaptic neuromodulation. To test whether the effects of arousal occur already in the retina, we recorded from retinal axons in the optic tract. We found that, in darkness, more than one third of the recorded axons was significantly correlated with running speed. Arousal had similar effects postsynaptically, in sSC neurons, independent of activity in V1, the other main source of visual inputs to colliculus. Optogenetic inactivation of V1 generally decreased activity in collicular neurons but did not diminish the effects of arousal. These results indicate that arousal modulates activity at every stage of the visual system. In the future, we will study the purpose and the underlying mechanisms of behavioural modulation in the early visual system
The emergence and modulation of time in neural circuits and behavior
Spontaneous behavior in animals and humans shows a striking amount of variability both in the spatial domain (which actions to choose) and temporal domain (when to act). Concatenating actions into sequences and behavioral plans reveals the existence of a hierarchy of timescales ranging from hundreds of milliseconds to minutes. How do multiple timescales emerge from neural circuit dynamics? How do circuits modulate temporal responses to flexibly adapt to changing demands? In this talk, we will present recent results from experiments and theory suggesting a new computational mechanism generating the temporal variability underlying naturalistic behavior and cortical activity. We will show how neural activity from premotor areas unfolds through temporal sequences of attractors, which predict the intention to act. These sequences naturally emerge from recurrent cortical networks, where correlated neural variability plays a crucial role in explaining the observed variability in action timing. We will then discuss how reaction times can be accelerated or slowed down via gain modulation, flexibly induced by neuromodulation or perturbations; and how gain modulation may control response timing in the visual cortex. Finally, we will present a new biologically plausible way to generate a reservoir of multiple timescales in cortical circuits.
Top-down neuromodulation of vasopressin cells in the olfactory bulb: implications for social discrimination
The emergence and modulation of time in neural circuits and behavior
Spontaneous behavior in animals and humans shows a striking amount of variability both in the spatial domain (which actions to choose) and temporal domain (when to act). Concatenating actions into sequences and behavioral plans reveals the existence of a hierarchy of timescales ranging from hundreds of milliseconds to minutes. How do multiple timescales emerge from neural circuit dynamics? How do circuits modulate temporal responses to flexibly adapt to changing demands? In this talk, we will present recent results from experiments and theory suggesting a new computational mechanism generating the temporal variability underlying naturalistic behavior. We will show how neural activity from premotor areas unfolds through temporal sequences of attractors, which predict the intention to act. These sequences naturally emerge from recurrent cortical networks, where correlated neural variability plays a crucial role in explaining the observed variability in action timing. We will then discuss how reaction times in these recurrent circuits can be accelerated or slowed down via gain modulation, induced by neuromodulation or perturbations. Finally, we will present a general mechanism producing a reservoir of multiple timescales in recurrent networks.
Unique Molecular Regulation of Prefrontal Cortex Confers Vulnerability to Cognitive Disorders
The Arnsten lab studies molecular influences on the higher cognitive circuits of the dorsolateral prefrontal cortex (dlPFC), in order to understand mechanisms affecting working memory at the cellular and behavioral levels, with the overarching aim of identifying the actions that render the dlPFC so vulnerable in cognitive disorders. Her lab has shown that the dlPFC has unique neurotransmission and neuromodulation compared to the classic actions found in the primary visual cortex, including mechanisms to rapidly weaken PFC connections during uncontrollable stress. Reduced regulation of these stress pathways due to genetic or environmental insults contributes to dlPFC dysfunction in cognitive disorders, including calcium dysregulation and tau phosphorylation in the aging association cortex. Understanding these unique mechanisms has led to the development of a new treatment, IntunivTM, for a variety of PFC disorders.
Circuit mechanisms underlying the dynamic control of cortical processing by subcortical neuromodulators
Behavioral states such as arousal and attention can have profound effects on sensory processing, determining how – sometimes whether – a stimulus is processed. This state-dependence is believed to arise, at least in part, as a result of inputs to cortex from subcortical structures that release neuromodulators such as acetylcholine, noradrenaline, and serotonin, often non-synaptically. The mechanisms that underlie the interaction between these “wireless” non-synaptic signals and the “wired” cortical circuit are not well understood. Furthermore, neuromodulatory signaling is traditionally considered broad in its impact across cortex (within a species) and consistent in its form and function across species (at least in mammals). The work I will present approaches the challenge of understanding neuromodulatory action in the cortex from a number of angles: anatomy, physiology, pharmacology, and chemistry. The overarching goal of our effort is to elucidate the mechanisms behind local neuromodulation in the cortex of non-human primates, and to reveal differences in structure and function across cortical model systems.
Differential Resilience of Neurons and Networks with Similar Behavior to Perturbation
Both computational and experimental results in single neurons and small networks demonstrate that very similar network function can result from quite disparate sets of neuronal and network parameters. Using the crustacean stomatogastric nervous system, we study the influence of these differences in underlying structure on differential resilience of individuals to a variety of environmental perturbations, including changes in temperature, pH, potassium concentration and neuromodulation. We show that neurons with many different kinds of ion channels can smoothly move through different mechanisms in generating their activity patterns, thus extending their dynamic range.
Differential Resilience of Neurons and Networks with Similar Behavior to Perturbation. (Simultaneous translation to Spanish)
Both computational and experimental results in single neurons and small networks demonstrate that very similar network function can result from quite disparate sets of neuronal and network parameters. Using the crustacean stomatogastric nervous system, we study the influence of these differences in underlying structure on differential resilience of individuals to a variety of environmental perturbations, including changes in temperature, pH, potassium concentration and neuromodulation. We show that neurons with many different kinds of ion channels can smoothly move through different mechanisms in generating their activity patterns, thus extending their dynamic range. The talk will be simultaneously translated to spanish by the interpreter Liliana Viera, MSc. Los resultados tanto computacionales como experimentales en neuronas individuales y redes pequeñas demuestran que funcionamientos de redes muy similares pueden pueden resultar de conjuntos bastante dispares de parámetros neuronales y de las redes. Utilizando el sistema nervioso estomatogástrico de los crustáceos, estudiamos la influencia de estas diferencias en la estructura subyacente en la resistencia diferencial de los individuos a una variedad de perturbaciones ambientales, incluidos los cambios de temperatura, pH, concentración de potasio y neuromodulación. Mostramos que neuronas con muchos tipos diferentes de canales iónicos pueden moverse suavemente a través de diferentes mecanismos para generar sus patrones de actividad, extendiendo así su rango dinámico. La conferencia será traducida simultáneamente al español por la intérprete Liliana Viera MSc.
Untitled Seminar
Sodium channel dysfunction in neurodevelopmental disorders
Enhancing learning through neuromodulation-aware spiking neural networks
Bernstein Conference 2024
Modeling and optimization for neuromodulation in spinal cord stimulation
COSYNE 2022
Modeling and optimization for neuromodulation in spinal cord stimulation
COSYNE 2022
Neuromodulation as a path along the model manifold for spiking networks
COSYNE 2022
Neuromodulation as a path along the model manifold for spiking networks
COSYNE 2022
Neuromodulation of synaptic plasticity rules avoids homeostatic reset of synaptic weights during switches in brain states
COSYNE 2022
Neuromodulation of synaptic plasticity rules avoids homeostatic reset of synaptic weights during switches in brain states
COSYNE 2022
Human Spinal Epidural Neuromodulation Modeling and Stimulation Effect Prediction
COSYNE 2023
Ethological foraging fingerprints reveal heterogeneous effects of serotonergic neuromodulation
COSYNE 2025
Modeling rapid neuromodulation in the cortex-basal ganglia-thalamus loop
COSYNE 2025
Cholinergic neuromodulation of processing sensory and reinforcement signals
FENS Forum 2024
Combinatorial architecture of circuit neuromodulation
FENS Forum 2024
Development of a next-generation bidirectional neurobiohybrid interface with optimized energy efficiency enabling real-time adaptive neuromodulation
FENS Forum 2024
Lateralization of motor responses following focused ultrasound neuromodulation of the motor cortex and thalamus in awake mice
FENS Forum 2024
On the way to layer-by-layer infrared neuromodulation: Presentation and functional characterisation of an intracortical optrode needle featured with a micromirror tip ending
FENS Forum 2024
Low-frequency cortical activity changes generated by continuous wave infrared neuromodulation recorded with an intracortical optrode during anesthesia
FENS Forum 2024
Neuromodulation robustly tunes rhythmic patterns in a fixed connectome: Application to gait control
FENS Forum 2024
Neuromodulation signaling in the nucleus accumbens during maternal behavior
FENS Forum 2024
Neuromodulation in The Virtual Brain: Introducing dopamine dynamics
FENS Forum 2024
Neuromodulation with DBS and FUS: Ephys effects in an animal model of depression
FENS Forum 2024
Non-canonical adrenergic neuromodulation of motoneuron intrinsic excitability through β-receptors in wild-type and SOD1 (G93A) mice
FENS Forum 2024
Noradrenergic neuromodulation of neuronal dynamics and behavior
FENS Forum 2024
A novel 3D-printed micro-drive system for infrared neuromodulation and electrophysiological recording in freely roaming rodents
FENS Forum 2024
Sleep-spindle triggered closed-loop neuromodulation of pathological anxiety in rats
FENS Forum 2024
Solid-state nanopores for spatially resolved chemical neuromodulation
FENS Forum 2024
Transcranial ultrasound neuromodulation induces metabolic and resting-state changes in amygdala
FENS Forum 2024
Understanding neuromodulation pathways in tDCS: Brainstem recording following DC-TNS in anesthetized rats
FENS Forum 2024
Wireless deep brain stimulation with magnetoelectric nanoparticle-based neuromodulation approach
FENS Forum 2024