mood disorders

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.

Applied cognitive neuroscience to improve learning and therapeutics

Advancements in cognitive neuroscience have provided profound insights into the workings of the human brain and the methods used offer opportunities to enhance performance, cognition, and mental health. Drawing upon interdisciplinary collaborations in the University of California San Diego, Human Performance Optimization Lab, this talk explores the application of cognitive neuroscience principles in three domains to improve human performance and alleviate mental health challenges. The first section will discuss studies addressing the role of vision and oculomotor function in athletic performance and the potential to train these foundational abilities to improve performance and sports outcomes. The second domain considers the use of electrophysiological measurements of the brain and heart to detect, and possibly predict, errors in manual performance, as shown in a series of studies with surgeons as they perform robot-assisted surgery. Lastly, findings from clinical trials testing personalized interventional treatments for mood disorders will be discussed in which the temporal and spatial parameters of transcranial magnetic stimulation (TMS) are individualized to test if personalization improves treatment response and can be used as predictive biomarkers to guide treatment selection. Together, these translational studies use the measurement tools and constructs of cognitive neuroscience to improve human performance and well-being.

From the guts to the brain through adaptive immunity in the prevention of Alzheimer’ disease

Dr. Pasinetti is the Saunders Family Chair and Professor of Neurology at Icahn School of medicine at Mount Sinai, New York. His studies allowed him to develop novel therapeutic approaches through investigation of preventable risk factors including mood disorders in the promotion of resilience against neurodegenerative disorder. In his presentation Dr. Pasinetti will discuss novel concepts about the gut-brain axis in mechanisms associated to peripheral adaptive immunity as therapeutic targets to mitigate the onset and the progression of Alzheimer’s disease and other form of dementia.

Ebselen: a lithium-mimetic without lithium side-effects?

Development of new medications for mental health conditions is a pressing need given the high proportion of people not responding to available treatments. We hope that presenting ebselen to a wider audience will inspire further studies on this promising agent with a benign side-effects profile. Laboratory research, animal research and human studies suggest that ebselen shares many features with the mood stabilising drug lithium, creating a promise of a drug that would have a similar clinical effect but without lithium’s troublesome side-effect profile and toxicity. Both drugs have a common biological target, inositol monophosphatase, whose inhibition is thought key to lithium’s therapeutic effect. Both drugs have neuroprotective action and reduce oxidative stress. In animal studies, ebselen affected neurotransmitters involved in the development of mental health symptoms, and in particular, produced effects of serotonin function very similar to lithium. Both ebselen and lithium share behavioural effects: antidepressant-like effects in rodent models of depression and decrease in behavioural impulsivity, a property associated with lithium's anti-suicidal action. Human neuropsychological studies support an antidepressant profile for ebselen based on its positive impact on emotional processing and reward seeking. Our group currently is exploring ebselen’s effects in patients with mood disorders. A completed ‘add-on’ clinical trial in mania showed ebselen’s superiority over placebo after three weeks of treatment. Our ongoing experimental research explores ebselen’s antidepressant profile in patients with treatment resistant depression. If successful, this will lead to a clinical trial of ebselen as an antidepressant augmentation agent, similar to lithium.

Multimodal tracking of motor activity, sleep and mood

This talk will (1) describe patterns and correlates of objectively assessed motor activity (2) present findings on the inter-relationships among motor activity, sleep and circadian rhythms and mood disorders; (3) describe potential of cross species studies of motor activity and related systems to inform human chronobiology research

The ubiquity of opportunity cost: Foraging and beyond

A key insight from the foraging literature is the importance of assessing the overall environmental quality — via global reward rate or similar measures, which capture the opportunity cost of time and can guide behavioral allocation toward relatively richer options. Meanwhile, the majority of research in decision neuroscience and computational psychiatry has focused instead on how choices are guided by much more local, event-locked evaluations: of individual situations, actions, or outcomes. I review a combination of research and theoretical speculation from my lab and others that emphasizes the role of foraging's average rewards and opportunity costs in a much larger range of decision problems, including risk, time discounting, vigor, cognitive control, and deliberation. The broad range of behaviors affected by this type of evaluation gives a new theoretical perspective on the effects of stress and autonomic mobilization, and on mood and the broad range of symptoms associated with mood disorders.

Towards better interoceptive biomarkers in computational psychiatry

Empirical evidence and theoretical models both increasingly emphasize the importance of interoceptive processing in mental health. Indeed, many mood and psychiatric disorders involve disturbed feelings and/or beliefs about the visceral body. However, current methods to measure interoceptive ability are limited in a number of ways, restricting the utility and interpretation of interoceptive biomarkers in psychiatry. I will present some newly developed measures and models which aim to improve our understanding of disordered brain-body interaction in psychiatric illnesses.

‘Optimistic’ and ‘pessimistic’ decision-making as an indicator of animal emotion and welfare

Reliable and validated measures of emotion in animals are of great import; they are crucial to better understanding and developing treatments for human mood disorders, and they are necessary for ensuring good animal welfare. We have developed a novel measure of emotion in animals that is grounded in theory and psychological research – decision-making under ambiguity. Specifically, we consider that more ‘optimistic’ decisions about ambiguous stimuli reflect more positive emotional states, while the opposite is true for more ‘pessimistic’ decisions. In this talk, we will outline the background behind and implementation of this measure, meta-analyses that have been conducted to validate the measure, and discuss how computational modelling has been used to further understand the cognitive processes underlying ‘optimistic’ and ‘pessimistic’ decision-making as an indicator of animal emotion and welfare.

Synergistic effects of intranasally administered GALR2 and Y1R agonists on cognitive and mood-related behaviors in adult rats: Implications for neurodegenerative and mood disorders

FENS Forum 2024

Mir-34 family is involved in Chronic Social Defeat-induced vulnerability to mood disorders and cardiac mitochondrial dysfunctions

Cortical changes in perineuronal nets and parvalbumin interneurons in chronic pain-induced mood disorders

FENS Forum 2024

A key role of regular firing cells from central amygdala in mood disorders

FENS Forum 2024