Seminars

Affectively charged analogies are commonly used in literature and art, but also in politics and argumentation. There are reasons to think we may process these analogies differently. Notably, analogical reasoning is a complex process that requires the use of cognitive resources, which are limited. In the presence of affectively charged content, some of these resources might be directed towards affective processing and away from analogical reasoning. To investigate this idea, I investigated effects of affective charge on differences in brain activity evoked by sound versus unsound analogies. The presentation will detail the methods and results for two such experiments, one in which participants saw analogies formed of neutral and negative words and one in which they were created by combining conditioned symbols. I will also briefly discuss future research aiming to investigate the effects of analogical reasoning on brain activity related to affective processing.

The primary motor cortex (M1) is a major output center for movement execution and motor learning, and its dysfunction contributes to the pathophysiology of Parkinson’s disease (PD). While human studies have indicated that a loss of midbrain dopamine neurons alters M1 activation, the mechanisms underlying this phenomenon remain unclear. Using a mouse model of PD, we uncovered several shifts within M1 circuitry following dopamine depletion, including impaired excitation by thalamocortical afferents and altered excitability. Our findings add to the growing body of literature highlighting M1 as a major contributor in PD, and provide targeted neural substrates for possible therapeutic interventions.

Nearly all motivated behaviors require the ability to associate outcomes with specific actions and make adaptive decisions about future behavior. The nucleus accumbens (NAc) is integrally involved in these processes. The NAc is a heterogeneous population primarily composed of D1 and D2 medium spiny projection (MSN) neurons that are thought to have opposed roles in behavior, with D1 MSNs promoting reward and D2 MSNs promoting aversion. Here we examined what types of information are encoded by the D1 and D2 MSNs using optogenetics, fiber photometry, and cellular resolution calcium imaging. First, we showed that mice responded for optical self-stimulation of both cell types, suggesting D2-MSN activation is not inherently aversive. Next, we recorded population and single cell activity patterns of D1 and D2 MSNs during reinforcement as well as Pavlovian learning paradigms that allow dissociation of stimulus value, outcome, cue learning, and action. We demonstrated that D1 MSNs respond to the presence and intensity of unconditioned stimuli – regardless of value. Conversely, D2 MSNs responded to the prediction of these outcomes during specific cues. Overall, these results provide foundational evidence for the discrete aspects of information that are encoded within the NAc D1 and D2 MSN populations. These results will significantly enhance our understanding of the involvement of the NAc MSNs in learning and memory as well as how these neurons contribute to the development and maintenance of substance use disorders.

To efficiently process sensory information, the brain relies on statistical regularities in the input. While generally improving the reliability of sensory estimates, this strategy also induces perceptual illusions that help reveal the underlying computational principles. Focusing on auditory and visual perception, in my talk I will describe how the brain exploits statistical regularities within and across the senses for the perception space, time and multisensory integration. In particular, I will show how results from a series of psychophysical experiments can be interpreted in the light of Bayesian Decision Theory, and I will demonstrate how such canonical computations can be implemented into simple and biologically plausible neural circuits. Finally, I will show how such principles of sensory information processing can be leveraged in virtual and augmented reality to overcome display limitations and expand human perception.

It has long been assumed that certain “basic” emotions emerge from anatomically ingrained circuits. Yet growing research suggests that emotions emerge from more basic networks that comprise the brain’s basic functional architecture. In this talk, I’ll discuss evidence that human emotional experiences are associated with the co-activation of broadscale networks subserving psychological functions that are not specific to emotion.

In behaving rodents, CA1 pyramidal neurons receive spatially-tuned depolarizing synaptic input while traversing a specific location within an environment called its place. Midbrain dopamine neurons participate in reinforcement learning, and bursts of action potentials riding a depolarizing wave of synaptic input signal rewards and reward expectation. Interestingly, slice electrophysiology in vitro shows that both types of cells exhibit a pronounced reduction in firing rate (adaptation) and even cessation of firing during sustained depolarization. We included a five state Markov model of NaV1.6 (for CA1) and NaV1.2 (for dopamine neurons) respectively, in computational models of these two types of neurons. Our simulations suggest that long-term inactivation of this channel is responsible for the adaptation in CA1 pyramidal neurons, in response to triangular depolarizing current ramps. We also show that the differential contribution of slow inactivation in two subpopulations of midbrain dopamine neurons can account for their different dynamic ranges, as assessed by their responses to similar depolarizing ramps. These results suggest long-term inactivation of the sodium channel is a general mechanism for adaptation.

Circadian clocks dominate our lives. By creating and distributing an internal representation of 24-hour solar time, they prepare us, and thereby adapt us, to the daily and seasonal world. Jet-lag is an obvious indicator of what can go wrong when such adaptation is disrupted acutely. More seriously, the growing prevalence of rotational shift-work which runs counter to our circadian life, is a significant chronic challenge to health, presenting as increased incidence of systemic conditions such as metabolic and cardiovascular disease. Added to this, circadian and sleep disturbances are a recognised feature of various neurological and psychiatric conditions, and in some cases may contribute to disease progression. The “head ganglion” of the circadian system is the suprachiasmatic nucleus (SCN) of the hypothalamus. It synchronises the, literally, innumerable cellular clocks across the body, to each other and to solar time. Isolated in organotypic slice culture, it can maintain precise, high-amplitude circadian cycles of neural activity, effectively, indefinitely, just as it does in vivo. How is this achieved: how does this clock in a dish work? This presentation will consider SCN time-keeping at the level of molecular feedback loops, neuropeptidergic networks and neuron-astrocyte interactions.

Exposure to sensory regularities in the environment induces the human brain to form expectations about incoming stimuli and remains partially preserved in the absence of consciousness (i.e. coma and sleep). While regularity often refers to stimuli presented at a fixed pace, we recently explored whether auditory prediction extends to pseudo-regular sequences where sensory prediction is induced by locking sound onsets to heartbeat signals and whether it can occur across vigilance states. In a series of experiments in healthy volunteers, we found neural and cardiac evidence of auditory prediction during heartbeat-based auditory regularities in wakefulness and N2 sleep. This process could represent an important mechanism for detecting unexpected stimuli in the environment even in states of limited conscious and attentional resources.

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.

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.

2 Keynote lectures :“Homeostatic control of sleep in the fly"and “Management of Intracerebral Haemorrhage – where is the evidence?” and 2 sessions: "Cortical top-down information processing” and “Virtual/augmented reality and its implications for the clinic”

Neuroplasticity is a fundamental property of the nervous system that is maximal early in life, within a specific temporal window called critical period. However, it is still unclear to which extent the plastic potential of the visual cortex is retained in adulthood. We have surprisingly revealed residual ocular dominance plasticity in adult humans by showing that short-term monocular deprivation unexpectedly boosts the deprived eye (both at the perceptual and at the neural level), reflecting homeostatic plasticity. This effect is accompanied by a decrease of GABAergic inhibition in the primary visual cortex and can be modulated by non-visual factors (motor activity and motor plasticity). Finally, we have found that cross-modal plasticity is preserved in adult normal-sighted humans, as short-term monocular deprivation can alter early visuo-tactile interactions. Taken together, these results challenge the classical view of a hard-wired adult visual cortex, indicating that homeostatic plasticity can be reactivated in adult humans.