Modulation
modulation
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.
Neural mechanisms of optimal performance
When we attend a demanding task, our performance is poor at low arousal (when drowsy) or high arousal (when anxious), but we achieve optimal performance at intermediate arousal. This celebrated Yerkes-Dodson inverted-U law relating performance and arousal is colloquially referred to as being "in the zone." In this talk, I will elucidate the behavioral and neural mechanisms linking arousal and performance under the Yerkes-Dodson law in a mouse model. During decision-making tasks, mice express an array of discrete strategies, whereby the optimal strategy occurs at intermediate arousal, measured by pupil, consistent with the inverted-U law. Population recordings from the auditory cortex (A1) further revealed that sound encoding is optimal at intermediate arousal. To explain the computational principle underlying this inverted-U law, we modeled the A1 circuit as a spiking network with excitatory/inhibitory clusters, based on the observed functional clusters in A1. Arousal induced a transition from a multi-attractor (low arousal) to a single attractor phase (high arousal), and performance is optimized at the transition point. The model also predicts stimulus- and arousal-induced modulations of neural variability, which we confirmed in the data. Our theory suggests that a single unifying dynamical principle, phase transitions in metastable dynamics, underlies both the inverted-U law of optimal performance and state-dependent modulations of neural variability.
SWEBAGS conference 2024: Shared network mechanisms of dopamine and deep brain stimulation for the treatment of Parkinson’s disease: From modulation of oscillatory cortex – basal ganglia communication to intelligent clinical brain computer interfaces
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!
Time perception in film viewing as a function of film editing
Filmmakers and editors have empirically developed techniques to ensure the spatiotemporal continuity of a film's narration. In terms of time, editing techniques (e.g., elliptical, overlapping, or cut minimization) allow for the manipulation of the perceived duration of events as they unfold on screen. More specifically, a scene can be edited to be time compressed, expanded, or real-time in terms of its perceived duration. Despite the consistent application of these techniques in filmmaking, their perceptual outcomes have not been experimentally validated. Given that viewing a film is experienced as a precise simulation of the physical world, the use of cinematic material to examine aspects of time perception allows for experimentation with high ecological validity, while filmmakers gain more insight on how empirically developed techniques influence viewers' time percept. Here, we investigated how such time manipulation techniques of an action affect a scene's perceived duration. Specifically, we presented videos depicting different actions (e.g., a woman talking on the phone), edited according to the techniques applied for temporal manipulation and asked participants to make verbal estimations of the presented scenes' perceived durations. Analysis of data revealed that the duration of expanded scenes was significantly overestimated as compared to that of compressed and real-time scenes, as was the duration of real-time scenes as compared to that of compressed scenes. Therefore, our results validate the empirical techniques applied for the modulation of a scene's perceived duration. We also found interactions on time estimates of scene type and editing technique as a function of the characteristics and the action of the scene presented. Thus, these findings add to the discussion that the content and characteristics of a scene, along with the editing technique applied, can also modulate perceived duration. Our findings are discussed by considering current timing frameworks, as well as attentional saliency algorithms measuring the visual saliency of the presented stimuli.
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!
Visual mechanisms for flexible behavior
Perhaps the most impressive aspect of the way the brain enables us to act on the sensory world is its flexibility. We can make a general inference about many sensory features (rating the ripeness of mangoes or avocados) and map a single stimulus onto many choices (slicing or blending mangoes). These can be thought of as flexibly mapping many (features) to one (inference) and one (feature) to many (choices) sensory inputs to actions. Both theoretical and experimental investigations of this sort of flexible sensorimotor mapping tend to treat sensory areas as relatively static. Models typically instantiate flexibility through changing interactions (or weights) between units that encode sensory features and those that plan actions. Experimental investigations often focus on association areas involved in decision-making that show pronounced modulations by cognitive processes. I will present evidence that the flexible formatting of visual information in visual cortex can support both generalized inference and choice mapping. Our results suggest that visual cortex mediates many forms of cognitive flexibility that have traditionally been ascribed to other areas or mechanisms. Further, we find that a primary difference between visual and putative decision areas is not what information they encode, but how that information is formatted in the responses of neural populations, which is related to difference in the impact of causally manipulating different areas on behavior. This scenario allows for flexibility in the mapping between stimuli and behavior while maintaining stability in the information encoded in each area and in the mappings between groups of neurons.
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.
Circadian modulation by time-restricted feeding rescues brain pathology and improves memory in mouse models of Alzheimer’s disease
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!
Rhythms for cognition: Learning, routing and top-down modulation
Location, time and type of epileptic activity influence how sleep modulates epilepsy
Sleep and epilepsy are tightly interconnected: On the one hand disturbed sleep is known to negatively affect epilepsy, whereas on the other hand epilepsy negatively impacts sleep. In this talk, we leverage on the unique opportunity provided by simultaneous stereo-EEG and sleep recordings to disentangle these relationships. We will discuss latest evidence on if anatomy (temporal vs. extratemporal), time (early vs. late sleep), and type of epileptic activity (ictal vs. interictal) influence how epileptic activity is modulated by sleep. After this talk, attendees will have a more nuanced understanding of the contributions of location, time and type of epileptic activity in the relationship between sleep and epilepsy.
Diffuse coupling in the brain - A temperature dial for computation
The neurobiological mechanisms of arousal and anesthesia remain poorly understood. Recent evidence highlights the key role of interactions between the cerebral cortex and the diffusely projecting matrix thalamic nuclei. Here, we interrogate these processes in a whole-brain corticothalamic neural mass model endowed with targeted and diffusely projecting thalamocortical nuclei inferred from empirical data. This model captures key features seen in propofol anesthesia, including diminished network integration, lowered state diversity, impaired susceptibility to perturbation, and decreased corticocortical coherence. Collectively, these signatures reflect a suppression of information transfer across the cerebral cortex. We recover these signatures of conscious arousal by selectively stimulating the matrix thalamus, recapitulating empirical results in macaque, as well as wake-like information processing states that reflect the thalamic modulation of largescale cortical attractor dynamics. Our results highlight the role of matrix thalamocortical projections in shaping many features of complex cortical dynamics to facilitate the unique communication states supporting conscious awareness.
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!
The role of sub-population structure in computations through neural dynamics
Neural computations are currently conceptualised using two separate approaches: sorting neurons into functional sub-populations or examining distributed collective dynamics. Whether and how these two aspects interact to shape computations is currently unclear. Using a novel approach to extract computational mechanisms from recurrent networks trained on neuroscience tasks, we show that the collective dynamics and sub-population structure play fundamentally complementary roles. Although various tasks can be implemented in networks with fully random population structure, we found that flexible input–output mappings instead require a non-random population structure that can be described in terms of multiple sub-populations. Our analyses revealed that such a sub-population organisation enables flexible computations through a mechanism based on gain-controlled modulations that flexibly shape the collective dynamics.
Microbial modulation of zebrafish behavior and brain development
There is growing recognition that host-associated microbiotas modulate intrinsic neurodevelopmental programs including those underlying human social behavior. Despite this awareness, the fundamental processes are generally not understood. We discovered that the zebrafish microbiota is necessary for normal social behavior. By examining neuronal correlates of behavior, we found that the microbiota restrains neurite complexity and targeting of key forebrain neurons within the social behavior circuitry. The microbiota is also necessary for both localization and molecular functions of forebrain microglia, brain-resident phagocytes that remodel neuronal arbors. In particular, the microbiota promotes expression of complement signaling pathway components important for synapse remodeling. Our work provides evidence that the microbiota modulates zebrafish social behavior by stimulating microglial remodeling of forebrain circuits during early neurodevelopment and suggests molecular pathways for therapeutic interventions during atypical neurodevelopment.
Distinct contributions of different anterior frontal regions to rule-guided decision-making in primates: complementary evidence from lesions, electrophysiology, and neurostimulation
Different prefrontal areas contribute in distinctly different ways to rule-guided behaviour in the context of a Wisconsin Card Sorting Test (WCST) analog for macaques. For example, causal evidence from circumscribed lesions in NHPs reveals that dorsolateral prefrontal cortex (dlPFC) is necessary to maintain a reinforced abstract rule in working memory, orbitofrontal cortex (OFC) is needed to rapidly update representations of rule value, and the anterior cingulate cortex (ACC) plays a key role in cognitive control and integrating information for correct and incorrect trials over recent outcomes. Moreover, recent lesion studies of frontopolar cortex (FPC) suggest it contributes to representing the relative value of unchosen alternatives, including rules. Yet we do not understand how these functional specializations relate to intrinsic neuronal activities nor the extent to which these neuronal activities differ between different prefrontal regions. After reviewing the aforementioned causal evidence I will present our new data from studies using multi-area multi-electrode recording techniques in NHPs to simultaneously record from four different prefrontal regions implicated in rule-guided behaviour. Multi-electrode micro-arrays (‘Utah arrays’) were chronically implanted in dlPFC, vlPFC, OFC, and FPC of two macaques, allowing us to simultaneously record single and multiunit activity, and local field potential (LFP), from all regions while the monkey performs the WCST analog. Rule-related neuronal activity was widespread in all areas recorded but it differed in degree and in timing between different areas. I will also present preliminary results from decoding analyses applied to rule-related neuronal activities both from individual clusters and also from population measures. These results confirm and help quantify dynamic task-related activities that differ between prefrontal regions. We also found task-related modulation of LFPs within beta and gamma bands in FPC. By combining this correlational recording methods with trial-specific causal interventions (electrical microstimulation) to FPC we could significantly enhance and impair animals performance in distinct task epochs in functionally relevant ways, further consistent with an emerging picture of regional functional specialization within a distributed framework of interacting and interconnected cortical regions.
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!
Routing and modulation of retinal input to circuits underlying aversive behavior
Dynamic endocrine modulation of the nervous system
Sex hormones are powerful neuromodulators of learning and memory. In rodents and nonhuman primates estrogen and progesterone influence the central nervous system across a range of spatiotemporal scales. Yet, their influence on the structural and functional architecture of the human brain is largely unknown. Here, I highlight findings from a series of dense-sampling neuroimaging studies from my laboratory designed to probe the dynamic interplay between the nervous and endocrine systems. Individuals underwent brain imaging and venipuncture every 12-24 hours for 30 consecutive days. These procedures were carried out under freely cycling conditions and again under a pharmacological regimen that chronically suppresses sex hormone production. First, resting state fMRI evidence suggests that transient increases in estrogen drive robust increases in functional connectivity across the brain. Time-lagged methods from dynamical systems analysis further reveals that these transient changes in estrogen enhance within-network integration (i.e. global efficiency) in several large-scale brain networks, particularly Default Mode and Dorsal Attention Networks. Next, using high-resolution hippocampal subfield imaging, we found that intrinsic hormone fluctuations and exogenous hormone manipulations can rapidly and dynamically shape medial temporal lobe morphology. Together, these findings suggest that neuroendocrine factors influence the brain over short and protracted timescales.
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.
Circuit solutions for programming actions
The hippocampus is one of the few regions in the adult mammalian brain which is endowed with life-long neurogenesis. Despite intense investigation, it remains unclear how neurons newly-generated may retain unique functions that contribute to modulate hippocampal information processing and cognition. In this talk, I will present some recent findings revealing how enhanced forms of plasticity in adult-born neurons underlie the way they become incorporated into pre-existing networks in response to experience.
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!
A premotor amodal clock for rhythmic tapping
We recorded and analyzed the population activity of hundreds of neurons in the medial premotor areas (MPC) of rhesus monkeys performing an isochronous tapping task guided by brief flashing stimuli or auditory tones. The animals showed a strong bias towards visual metronomes, with rhythmic tapping that was more precise and accurate than for auditory metronomes. The population dynamics in state space as well as the corresponding neural sequences shared the following properties across modalities: the circular dynamics of the neural trajectories and the neural sequences formed a regenerating loop for every produced interval, producing a relative time representation; the trajectories converged in similar state space at tapping times while the moving bumps restart at this point, resetting the beat-based clock; the tempo of the synchronized tapping was encoded by a combination of amplitude modulation and temporal scaling in the neural trajectories. In addition, the modality induced a displacement in the neural trajectories in auditory and visual subspaces without greatly altering time keeping mechanism. These results suggest that the interaction between the amodal internal representation of pulse within MPC and a modality specific external input generates a neural rhythmic clock whose dynamics define the temporal execution of tapping using auditory and visual metronomes.
The Effects of Negative Emotions on Mental Representation of Faces
Face detection is an initial step of many social interactions involving a comparison between a visual input and a mental representation of faces, built from previous experience. Whilst emotional state was found to affect the way humans attend to faces, little research has explored the effects of emotions on the mental representation of faces. Here, we examined the specific perceptual modulation of geometric properties of the mental representations associated with state anxiety and state depression on face detection, and to compare their emotional expression. To this end, we used an adaptation of the reverse correlation technique inspired by Gosselin and Schyns’, (2003) ‘Superstitious Approach’, to construct visual representations of observers’ mental representations of faces and to relate these to their mental states. In two sessions, on separate days, participants were presented with ‘colourful’ noise stimuli and asked to detect faces, which they were told were present. Based on the noise fragments that were identified as faces, we reconstructed the pictorial mental representation utilised by each participant in each session. We found a significant correlation between the size of the mental representation of faces and participants’ level of depression. Our findings provide a preliminary insight about the way emotions affect appearance expectation of faces. To further understand whether the facial expressions of participants’ mental representations reflect their emotional state, we are conducting a validation study with a group of naïve observers who are asked to classify the reconstructed face images by emotion. Thus, we assess whether the faces communicate participants’ emotional states to others.
The role of population structure in computations through neural dynamics
Neural computations are currently investigated using two separate approaches: sorting neurons into functional subpopulations or examining the low-dimensional dynamics of collective activity. Whether and how these two aspects interact to shape computations is currently unclear. Using a novel approach to extract computational mechanisms from networks trained on neuroscience tasks, here we show that the dimensionality of the dynamics and subpopulation structure play fundamentally com- plementary roles. Although various tasks can be implemented by increasing the dimensionality in networks with fully random population structure, flexible input–output mappings instead require a non-random population structure that can be described in terms of multiple subpopulations. Our analyses revealed that such a subpopulation structure enables flexible computations through a mechanism based on gain-controlled modulations that flexibly shape the collective dynamics. Our results lead to task-specific predictions for the structure of neural selectivity, for inactivation experiments and for the implication of different neurons in multi-tasking.
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!
Hunger state-dependent modulation of decision-making in larval Drosophila
It is critical for all animals to make appropriate, but also flexible, foraging decisions, especially when facing starvation. Sensing olfactory information is essential to evaluate food quality before ingestion. Previously, we found that <i>Drosophila</i> larvae switch their response to certain odors from aversion to attraction when food deprived. The neural mechanism underlying this switch in behavior involves serotonergic modulation and reconfiguration of odor processing in the early olfactory sensory system. We now investigate if a change in hunger state also influences other behavioral decisions. Since it had been shown that fly larvae can perform cannibalism, we investigate the effect of food deprivation on feeding on dead conspecifics. We find that fed fly larvae rarely use dead conspecifics as a food source. However, food deprivation largely enhances this behavior. We will now also investigate the underlying neural mechanisms that mediate this enhancement and compare it to the already described mechanism for a switch in olfactory choice behavior. Generally, this flexibility in foraging behavior enables the larva to explore a broader range of stimuli and to expand their feeding choices to overcome starvation.
Invariant neural subspaces maintained by feedback modulation
This session is a double feature of the Cologne Theoretical Neuroscience Forum and the Institute of Neuroscience and Medicine (INM-6) Computational and Systems Neuroscience of the Jülich Research Center.
From Computation to Large-scale Neural Circuitry in Human Belief Updating
Many decisions under uncertainty entail dynamic belief updating: multiple pieces of evidence informing about the state of the environment are accumulated across time to infer the environmental state, and choose a corresponding action. Traditionally, this process has been conceptualized as a linear and perfect (i.e., without loss) integration of sensory information along purely feedforward sensory-motor pathways. Yet, natural environments can undergo hidden changes in their state, which requires a non-linear accumulation of decision evidence that strikes a tradeoff between stability and flexibility in response to change. How this adaptive computation is implemented in the brain has remained unknown. In this talk, I will present an approach that my laboratory has developed to identify evidence accumulation signatures in human behavior and neural population activity (measured with magnetoencephalography, MEG), across a large number of cortical areas. Applying this approach to data recorded during visual evidence accumulation tasks with change-points, we find that behavior and neural activity in frontal and parietal regions involved in motor planning exhibit hallmarks signatures of adaptive evidence accumulation. The same signatures of adaptive behavior and neural activity emerge naturally from simulations of a biophysically detailed model of a recurrent cortical microcircuit. The MEG data further show that decision dynamics in parietal and frontal cortex are mirrored by a selective modulation of the state of early visual cortex. This state modulation is (i) specifically expressed in the alpha frequency-band, (ii) consistent with feedback of evolving belief states from frontal cortex, (iii) dependent on the environmental volatility, and (iv) amplified by pupil-linked arousal responses during evidence accumulation. Together, our findings link normative decision computations to recurrent cortical circuit dynamics and highlight the adaptive nature of decision-related long-range feedback processing in the brain.
Canonical neural networks perform active inference
The free-energy principle and active inference have received a significant attention in the fields of neuroscience and machine learning. However, it remains to be established whether active inference is an apt explanation for any given neural network that actively exchanges with its environment. To address this issue, we show that a class of canonical neural networks of rate coding models implicitly performs variational Bayesian inference under a well-known form of partially observed Markov decision process model (Isomura, Shimazaki, Friston, Commun Biol, 2022). Based on the proposed theory, we demonstrate that canonical neural networks—featuring delayed modulation of Hebbian plasticity—can perform planning and adaptive behavioural control in the Bayes optimal manner, through postdiction of their previous decisions. This scheme enables us to estimate implicit priors under which the agent’s neural network operates and identify a specific form of the generative model. The proposed equivalence is crucial for rendering brain activity explainable to better understand basic neuropsychology and psychiatric disorders. Moreover, this notion can dramatically reduce the complexity of designing self-learning neuromorphic hardware to perform various types of tasks.
Sex Differences in Learning from Exploration
Sex-based modulation of cognitive processes could set the stage for individual differences in vulnerability to neuropsychiatric disorders. While value-based decision making processes in particular have been proposed to be influenced by sex differences, the overall correct performance in decision making tasks often show variable or minimal differences across sexes. Computational tools allow us to uncover latent variables that define different decision making approaches, even in animals with similar correct performance. Here, we quantify sex differences in mice in the latent variables underlying behavior in a classic value-based decision making task: a restless two-armed bandit. While male and female mice had similar accuracy, they achieved this performance via different patterns of exploration. Male mice tended to make more exploratory choices overall, largely because they appeared to get ‘stuck’ in exploration once they had started. Female mice tended to explore less but learned more quickly during exploration. Together, these results suggest that sex exerts stronger influences on decision making during periods of learning and exploration than during stable choices. Exploration during decision making is altered in people diagnosed with addictions, depression, and neurodevelopmental disabilities, pinpointing the neural mechanisms of exploration as a highly translational avenue for conferring sex-modulated vulnerability to neuropsychiatric diagnoses.
Unchanging and changing: hardwired taste circuits and their top-down control
The taste system detects 5 major categories of ethologically relevant stimuli (sweet, bitter, umami, sour and salt) and accordingly elicits acceptance or avoidance responses. While these taste responses are innate, the taste system retains a remarkable flexibility in response to changing external and internal contexts. Taste chemicals are first recognized by dedicated taste receptor cells (TRCs) and then transmitted to the cortex via a multi-station relay. I reasoned that if I could identify taste neural substrates along this pathway, it would provide an entry to decipher how taste signals are encoded to drive innate response and modulated to facilitate adaptive response. Given the innate nature of taste responses, these neural substrates should be genetically identifiable. I therefore exploited single-cell RNA sequencing to isolate molecular markers defining taste qualities in the taste ganglion and the nucleus of the solitary tract (NST) in the brainstem, the two stations transmitting taste signals from TRCs to the brain. How taste information propagates from the ganglion to the brain is highly debated (i.e., does taste information travel in labeled-lines?). Leveraging these genetic handles, I demonstrated one-to-one correspondence between ganglion and NST neurons coding for the same taste. Importantly, inactivating one ‘line’ did not affect responses to any other taste stimuli. These results clearly showed that taste information is transmitted to the brain via labeled lines. But are these labeled lines aptly adapted to the internal state and external environment? I studied the modulation of taste signals by conflicting taste qualities in the concurrence of sweet and bitter to understand how adaptive taste responses emerge from hardwired taste circuits. Using functional imaging, anatomical tracing and circuit mapping, I found that bitter signals suppress sweet signals in the NST via top-down modulation by taste cortex and amygdala of NST taste signals. While the bitter cortical field provides direct feedback onto the NST to amplify incoming bitter signals, it exerts negative feedback via amygdala onto the incoming sweet signal in the NST. By manipulating this feedback circuit, I showed that this top-down control is functionally required for bitter evoked suppression of sweet taste. These results illustrate how the taste system uses dedicated feedback lines to finely regulate innate behavioral responses and may have implications for the context-dependent modulation of hardwired circuits in general.
A transcriptomic axis predicts state modulation of cortical interneurons
Transcriptomics has revealed that cortical inhibitory neurons exhibit a great diversity of fine molecular subtypes, but it is not known whether these subtypes have correspondingly diverse activity patterns in the living brain. We show that inhibitory subtypes in primary visual cortex (V1) have diverse correlates with brain state, but that this diversity is organized by a single factor: position along their main axis of transcriptomic variation. We combined in vivo 2-photon calcium imaging of mouse V1 with a novel transcriptomic method to identify mRNAs for 72 selected genes in ex vivo slices. We classified inhibitory neurons imaged in layers 1-3 into a three-level hierarchy of 5 Subclasses, 11 Types, and 35 Subtypes using previously-defined transcriptomic clusters. Responses to visual stimuli differed significantly only across Subclasses, suppressing cells in the Sncg Subclass while driving cells in the other Subclasses. Modulation by brain state differed at all hierarchical levels but could be largely predicted from the first transcriptomic principal component, which also predicted correlations with simultaneously recorded cells. Inhibitory Subtypes that fired more in resting, oscillatory brain states have less axon in layer 1, narrower spikes, lower input resistance and weaker adaptation as determined in vitro and express more inhibitory cholinergic receptors. Subtypes firing more during arousal had the opposite properties. Thus, a simple principle may largely explain how diverse inhibitory V1 Subtypes shape state-dependent cortical processing.
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.
Astroglial modulation of the antidepressant action of deep brain and bright light stimulation
Even if major depression is now the most common of psychiatric disorders, successful antidepressant treatments are still difficult to achieve. Therefore, a better understanding of the mechanisms of action of current antidepressant treatments is needed to ultimately identify new targets and enhance beneficial effects. Given the intimate relationships between astrocytes and neurons at synapses and the ability of astrocytes to "sense" neuronal communication and release gliotransmitters, an attractive hypothesis is emerging stating that the effects of antidepressants on brain function could be, at least in part, modulated by direct influences of astrocytes on neuronal networks. We will present two preclinical studies revealing a permissive role of glia in the antidepressant response: i) Control of the antidepressant-like effects of rat prefrontal cortex Deep Brain Stimulation (DBS) by astroglia, ii) Modulation of antidepressant efficacy of Bright Light Stimulation (BLS) by lateral habenula astroglia. Therefore, it is proposed that an unaltered neuronal-glial system constitutes a major prerequisite to optimize antidepressant efficacy of DBS or BLS. Collectively, these results pave also the way to the development of safer and more effective antidepressant strategies.
Inter-individual variability in reward seeking and decision making: role of social life and consequence for vulnerability to nicotine
Inter-individual variability refers to differences in the expression of behaviors between members of a population. For instance, some individuals take greater risks, are more attracted to immediate gains or are more susceptible to drugs of abuse than others. To probe the neural bases of inter-individual variability we study reward seeking and decision-making in mice, and dissect the specific role of dopamine in the modulation of these behaviors. Using a spatial version of the multi-armed bandit task, in which mice are faced with consecutive binary choices, we could link modifications of midbrain dopamine cell dynamics with modulation of exploratory behaviors, a major component of individual characteristics in mice. By analyzing mouse behaviors in semi-naturalistic environments, we then explored the role of social relationships in the shaping of dopamine activity and associated beahviors. I will present recent data from the laboratory suggesting that changes in the activity of dopaminergic networks link social influences with variations in the expression of non-social behaviors: by acting on the dopamine system, the social context may indeed affect the capacity of individuals to make decisions, as well as their vulnerability to drugs of abuse, in particular nicotine.
Brain-body interactions that modulate fear
In most animals including in humans, emotions occur together with changes in the body, such as variations in breathing or heart rate, sweaty palms, or facial expressions. It has been suggested that this interoceptive information acts as a feedback signal to the brain, enabling adaptive modulation of emotions that is essential for survival. As such, fear, one of our basic emotions, must be kept in a functional balance to minimize risk-taking while allowing for the pursuit of essential needs. However, the neural mechanisms underlying this adaptive modulation of fear remain poorly understood. In this talk, I want to present and discuss the data from my PhD work where we uncover a crucial role for the interoceptive insular cortex in detecting changes in heart rate to maintain an equilibrium between the extinction and maintenance of fear memories in mice.
Probabilistic computation in natural vision
A central goal of vision science is to understand the principles underlying the perception and neural coding of the complex visual environment of our everyday experience. In the visual cortex, foundational work with artificial stimuli, and more recent work combining natural images and deep convolutional neural networks, have revealed much about the tuning of cortical neurons to specific image features. However, a major limitation of this existing work is its focus on single-neuron response strength to isolated images. First, during natural vision, the inputs to cortical neurons are not isolated but rather embedded in a rich spatial and temporal context. Second, the full structure of population activity—including the substantial trial-to-trial variability that is shared among neurons—determines encoded information and, ultimately, perception. In the first part of this talk, I will argue for a normative approach to study encoding of natural images in primary visual cortex (V1), which combines a detailed understanding of the sensory inputs with a theory of how those inputs should be represented. Specifically, we hypothesize that V1 response structure serves to approximate a probabilistic representation optimized to the statistics of natural visual inputs, and that contextual modulation is an integral aspect of achieving this goal. I will present a concrete computational framework that instantiates this hypothesis, and data recorded using multielectrode arrays in macaque V1 to test its predictions. In the second part, I will discuss how we are leveraging this framework to develop deep probabilistic algorithms for natural image and video segmentation.
Neuromodulation of inference and control in the cortical circuits
Invariant neural subspaces maintained by feedback modulation
Sensory systems reliably process incoming stimuli in spite of changes in context. Most recent models accredit this context invariance to an extraction of increasingly complex sensory features in hierarchical feedforward networks. Here, we study how context-invariant representations can be established by feedback rather than feedforward processing. We show that feedforward neural networks modulated by feedback can dynamically generate invariant sensory representations. The required feedback can be implemented as a slow and spatially diffuse gain modulation. The invariance is not present on the level of individual neurons, but emerges only on the population level. Mechanistically, the feedback modulation dynamically reorients the manifold of neural activity and thereby maintains an invariant neural subspace in spite of contextual variations. Our results highlight the importance of population-level analyses for understanding the role of feedback in flexible sensory processing.
Modulation of oligodendrocyte development and myelination by voltage-gated Ca++ channels
The oligodendrocyte generates CNS myelin, which is essential for normal nervous system function. Thus, investigating the regulatory and signaling mechanisms that control its differentiation and the production of myelin is relevant to our understanding of brain development and of adult pathologies such as multiple sclerosis. We have recently established that the activity of voltage-gated Ca++ channels is crucial for the adequate migration, proliferation and maturation of oligodendrocyte progenitor cells (OPCs). Furthermore, we have found that voltage-gated Ca++ channels that function in synaptic communication between neurons also mediate synaptic signaling between neurons and OPCs. Thus, we hypothesize that voltage-gated Ca++ channels are central components of OPC-neuronal synapses and are the principal ion channels mediating activity-dependent myelination.
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
Synergy of color and motion vision for detecting approaching objects in Drosophila
I am working on color vision in Drosophila, identifying behaviors that involve color vision and understanding the neural circuits supporting them (Longden 2016). I have a long-term interest in understanding how neural computations operate reliably under changing circumstances, be they external changes in the sensory context, or internal changes of state such as hunger and locomotion. On internal state-modulation of sensory processing, I have shown how hunger alters visual motion processing in blowflies (Longden et al. 2014), and identified a role for octopamine in modulating motion vision during locomotion (Longden and Krapp 2009, 2010). On responses to external cues, I have shown how one kind of uncertainty in the motion of the visual scene is resolved by the fly (Saleem, Longden et al. 2012), and I have identified novel cells for processing translation-induced optic flow (Longden et al. 2017). I like working with colleagues who use different model systems, to get at principles of neural operation that might apply in many species (Ding et al. 2016, Dyakova et al. 2015). I like work motivated by computational principles - my background is computational neuroscience, with a PhD on models of memory formation in the hippocampus (Longden and Willshaw, 2007).
Dynamic Neuromodulation
Neural Codes for Natural Behaviors in Flying Bats
This talk will focus on the importance of using natural behaviors in neuroscience research – the “Natural Neuroscience” approach. I will illustrate this point by describing studies of neural codes for spatial behaviors and social behaviors, in flying bats – using wireless neurophysiology methods that we developed – and will highlight new neuronal representations that we discovered in animals navigating through 3D spaces, or in very large-scale environments, or engaged in social interactions. In particular, I will discuss: (1) A multi-scale neural code for very large environments, which we discovered in bats flying in a 200-meter long tunnel. This new type of neural code is fundamentally different from spatial codes reported in small environments – and we show theoretically that it is superior for representing very large spaces. (2) Rapid modulation of position × distance coding in the hippocampus during collision-avoidance behavior between two flying bats. This result provides a dramatic illustration of the extreme dynamism of the neural code. (3) Local-but-not-global order in 3D grid cells – a surprising experimental finding, which can be explained by a simple physics-inspired model, which successfully describes both 3D and 2D grids. These results strongly argue against many of the classical, geometrically-based models of grid cells. (4) I will also briefly describe new results on the social representation of other individuals in the hippocampus, in a highly social multi-animal setting. The lecture will propose that neuroscience experiments – in bats, rodents, monkeys or humans – should be conducted under evermore naturalistic conditions.
Continual learning using dendritic modulations on view-invariant feedforward weights
Bernstein Conference 2024
Enhancing learning through neuromodulation-aware spiking neural networks
Bernstein Conference 2024
Homeostatic gain modulation drives changes in heterogeneity expressed by neural populations
Bernstein Conference 2024
Modeling HCN Channel-Mediated Modulation on Dendro-Somatic Electric Coupling in CA1 Pyramidal Cells
Bernstein Conference 2024
Modulation of Spike-timing-dependent Plasticity via the Interaction of Astrocyte-regulated D-serine with NMDA Receptors
Bernstein Conference 2024
Modulation of Spontaneous Activity Patterns in Developing Sensory Cortices via Inhibition
Bernstein Conference 2024
Neocortical Modulation of Sharp Waves in a Rate Model of CA3
Bernstein Conference 2024
Predicting V1 contextual modulation and neural tuning using a convolutional neural network
Bernstein Conference 2024
Synaptic modulation facilitates adaptation in cortical networks
Bernstein Conference 2024
Top-down modulation shapes timescales via synaptic plasticity in cortical circuits with multiple interneuron types
Bernstein Conference 2024
Contextual modulation of mesoscale functional connectivity
COSYNE 2022
Experience-Driven Rate Modulation is Reinstated During Hippocampal Replay
COSYNE 2022
Fine-tuning hierarchical circuits through learned stochastic co-modulation
COSYNE 2022
Fine-tuning hierarchical circuits through learned stochastic co-modulation
COSYNE 2022
VIP interneuron-mediated disinhibition does not interact with endogenous attention modulation in V1
COSYNE 2022
VIP interneuron-mediated disinhibition does not interact with endogenous attention modulation in V1
COSYNE 2022
Invariant neural subspaces maintained by feedback modulation
COSYNE 2022
Invariant neural subspaces maintained by feedback modulation
COSYNE 2022
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
Relating Divisive Normalization to Modulation of Correlated Variability in Primary Visual Cortex
COSYNE 2022
Relating Divisive Normalization to Modulation of Correlated Variability in Primary Visual Cortex
COSYNE 2022
Sensory specific modulation of neural variability facilitates perceptual inference
COSYNE 2022
Sensory specific modulation of neural variability facilitates perceptual inference
COSYNE 2022
Subcortical modulation of cortical dynamics for motor planning: a computational framework
COSYNE 2022
Subcortical modulation of cortical dynamics for motor planning: a computational framework
COSYNE 2022
Top-down modulation in canonical cortical circuits with inhibitory short-term plasticity
COSYNE 2022
Top-down modulation in canonical cortical circuits with inhibitory short-term plasticity
COSYNE 2022
A transcriptomic axis predicts state modulation of cortical interneurons
COSYNE 2022
A transcriptomic axis predicts state modulation of cortical interneurons
COSYNE 2022
Unifying model of contextual modulation with feedback from higher visual areas
COSYNE 2022
Unifying model of contextual modulation with feedback from higher visual areas
COSYNE 2022
Can a conserved transcriptomic axis predict state modulation of cortical interneurons?
COSYNE 2023
Dendritic modulation for multitask representation learning in deep feedforward networks
COSYNE 2023
Experience-dependent modulation of brain-wide visuomotor processing and behavior
COSYNE 2023
Bayesian inference and arousal modulation in spatial perception to mitigate stochasticity and volatility
Bernstein Conference 2024