Seminars

In this talk I will present data from imaging studies that we have been conducting for the past 20 years trying to shed light on migraine physiopathology, from anatomical and functional MRI to positron emission tomography.

There is an avalanche of new data on activity in neural networks and the biological brain, revealing the collective dynamics of vast numbers of neurons. In principle, these collective dynamics can be of almost arbitrarily high dimension, with many independent degrees of freedom — and this may reflect powerful capacities for general computing or information. In practice, neural datasets reveal a range of outcomes, including collective dynamics of much lower dimension — and this may reflect other desiderata for neural codes. For what networks does each case occur? We begin by exploring bottom-up mechanistic ideas that link tractable statistical properties of network connectivity with the dimension of the activity that they produce. We then cover “top-down” ideas that describe how features of connectivity and dynamics that impact dimension arise as networks learn to perform fundamental computational tasks.

Previous work looking at individual differences in face identity processing (FIP) has found that most commonly used lab-based performance assessments are unfortunately not sufficiently sensitive on their own for measuring performance in both the upper and lower tails of the general population simultaneously. So more recently, researchers have begun incorporating multiple testing procedures into their assessments. Still, though, the growing consensus seems to be that at the individual level, there is quite a bit of variability between test scores. The overall consequence of this is that extreme scores will still occur simply by chance in large enough samples. To mitigate this issue, our recent work has developed measures of intra-individual FIP consistency to refine selection of those with superior abilities (i.e. from the upper tail). For starters, we assessed consistency of face matching and recognition in neurotypical controls, and compared them to a sample of SRs. In terms of face matching, we demonstrated psychophysically that SRs show significantly greater consistency than controls in exploiting spatial frequency information than controls. Meanwhile, we showed that SRs’ recognition of faces is highly related to memorability for identities, yet effectively unrelated among controls. So overall, at the high end of the FIP spectrum, consistency can be a useful tool for revealing both qualitative and quantitative individual differences. Finally, in conjunction with collaborators from the Rheinland-Pfalz Police, we developed a pair of bespoke work samples to get bias-free measures of intraindividual consistency in current law enforcement personnel. Officers with higher composite scores on a set of 3 challenging FIP tests tended to show higher consistency, and vice versa. Overall, this suggests that not only is consistency a reasonably good marker of superior FIP abilities, but could present important practical benefits for personnel selection in many other domains of expertise.

Recent breakthroughs in neurobiology indicate that time is ripe to understand the cellular-level mechanisms of conscious experience. Accordingly, we have recently proposed that conscious processing depends on the integration between top-down and bottom-up information streams and that there exists a specific cellular mechanism that gates this integration. I will first describe this cellular mechanism and demonstrate how it controls signal propagation within the thalamocortical system. Then I will show how this cellular-level mechanism provides a natural explanation for why conscious experience is modulated by top-down processing. Besides shining new light on the neural basis of consciousness, this perspective unravels the mechanisms of internally generated perception, such as dreams, imagery, and hallucinations.

Local anesthetics decrease the excitability of all neurons by blocking voltage-gated sodium channels non-selectively. We have developed a technology to silence only those sensory neurons – the nociceptors – that trigger pain, itch, and cough. I will tell you why and how we devised the strategy, the way we showed that it works, and will also discuss its implications for treating multiple human disorders.

Menstruation is a normal physiological process in women occurring as a result of changes in two ovarian produced hormones – estrogen and progesterone. As a result of these fluctuations, women experience different symptoms in their bodies – their immune system changes (Sekigawa et al, 2004), there are changes in their cardiovascular and digestive system (Millikan, 2006), as well as skin (Hall and Phillips, 2005). But these hormone fluctuations produce major changes in their behavioral pattern as well causing: anxiety, sadness, heightened irritability and anger (Severino and Moline, 1995) which is usually classified as premenstrual syndrome (PMS). In some cases these symptoms severely impair women’s lives and professional help is required. The official diagnosis according to DSM-5 (2013) is premenstrual dysphoric disorder (PMDD). Despite its ubiquitous presence the origins of PMS and PMDD are poorly understood. Some efforts to understand the underlying brain state during the menstruation cycle were performed by using TMS (Smith et al, 1999; 2002; 2003; Inghilleri et al, 2004; Hausmann et al, 2006). But all of these experiments suffer from major shortcomings - no control groups and small number of subjects. Our plan is to address all of these shortcomings and make this the biggest (to our knowledge) experiment of its kind which will, hopefully, provide us with some much needed answers.

Many patients presenting to neurology either have primary sleep disorders or suffer from sleep comorbidity. Knowledge on the diagnosis, differential diagnostic considerations, and management of these disorders is therefore mandatory for the general neurologist. This comprehensive course may serve to fulfill part of the preparation requirements for trainees seeking to complete the Royal College Examinations in Neurology. This training course is for R4 and R5 residents in Canadian neurology training programs as well as neurologists.

Knowing where we are, where we have been, and where we are going is critical to many behaviors, including navigation and memory. One potential neuronal mechanism underlying this ability is phase precession, in which spatially tuned neurons represent sequences of positions by activating at progressively earlier phases of local network theta oscillations. Based on studies in rodents, researchers have hypothesized that phase precession may be a general neural pattern for representing sequential events for learning and memory. By recording human single-neuron activity during spatial navigation, we show that spatially tuned neurons in the human hippocampus and entorhinal cortex exhibit phase precession. Furthermore, beyond the neural representation of locations, we show evidence for phase precession related to specific goal states. Our find- ings thus extend theta phase precession to humans and suggest that this phenomenon has a broad func- tional role for the neural representation of both spatial and non-spatial information.

The Hsieh lab focuses on the mechanisms that promote neural stem cell self-renewal and differentiation in embryonic and adult brain. Using mouse models, video-EEG monitoring, viral techniques, and imaging/electrophysiological approaches, we elucidated many of the key transcriptional/epigenetic regulators of adult neurogenesis and showed aberrant new neuron integration in adult rodent hippocampus contribute to circuit disruption and seizure development. Building on this work, I will present our recent studies describing how GABA-mediated Ca2+ activity regulates the production of aberrant adult-born granule cells. In a new direction of my laboratory, we are using human induced pluripotent stem cells and brain organoid models as approaches to understand brain development and disease. Mutations in one gene, Aristaless-related homeobox (ARX), are of considerable interest since they are known to cause a common spectrum of neurodevelopmental disorders including epilepsy, autism, and intellectual disability. We have generated cortical and subpallial organoids from patients with poly-alanine expansion mutations in ARX. To understand the nature of ARX mutations in the organoid system, we are currently performing cellular, molecular, and physiological analyses. I will present these data to gain a comprehensive picture of the effect of ARX mutations in brain development. Since we do not understand how human brain development is affected by ARX mutations that contribute to epilepsy, we believe these studies will allow us to understand the mechanism of pathogenesis of ARX mutations, which has the potential to impact the diagnosis and care of patients.

In our everyday lives, we form connections and build up social networks that allow us to function successfully as individuals and as a society. Our social networks tend to include well-connected individuals who link us to other groups of people that we might otherwise have limited access to. In addition, we are more likely to befriend individuals who a) live nearby and b) have mutual friends. Interestingly, neurons tend to do the same…until development is perturbed. Just like social networks, neuronal networks require highly connected hubs to elicit efficient communication at minimal cost (you can’t befriend everybody you meet, nor can every neuron wire with every other!). This talk will cover some of Alex’s work showing that microscopic (cellular scale) brain networks inferred from spontaneous activity show similar complex topology to that previously described in macroscopic human brain scans. The talk will also discuss what happens when neurodevelopment is disrupted in the case of a monogenic disorder called Rett Syndrome. This will include simulations of neuronal activity and the effects of manipulation of model parameters as well as what happens when we manipulate real developing networks using optogenetics. If functional development can be restored in atypical networks, this may have implications for treatment of neurodevelopmental disorders like Rett Syndrome.

In this talk I’ll discuss our recent work on how visual and auditory cues to space are integrated as we move. There are at least 3 reasons why this turns out to be a difficult problem for the brain to solve (and us to understand!). First, vision and hearing start off in different coordinates (eye-centred vs head-centred), so they need a common reference frame in which to communicate. By preventing eye and head movements, this problem has been neatly sidestepped in the literature, yet self-movement is the norm. Second, self-movement creates visual and auditory image motion. Correct interpretation therefore requires some form of compensation. Third, vision and hearing encode motion in very different ways: vision contains dedicated motion detectors sensitive to speed, whereas hearing does not. We propose that some (all?) of these problems could be solved by considering the perception of audiovisual space as the integration of separate body-centred visual and auditory cues, the latter formed by integrating image motion with motor system signals and vestibular information. To test this claim, we use a classic cue integration framework, modified to account for cues that are biased and partially correlated. We find good evidence for the model based on simple judgements of audiovisual motion within a circular array of speakers and LEDs that surround the participant while they execute self-controlled head movement.

Neuronal dendritic trees display a wide range of nonlinear input integrations due to their voltage-dependent active calcium channels. We reveal that in vivo-like fluctuating input enhances nonlinearity substantially in a single dendritic compartment and shifts the input-output relation to exhibiting nonmonotonous or bistable dynamics. In particular, with the slow activation of calcium dynamics, we analyze noise-induced bistability and its timescales. We show bistability induces long-timescale fluctuation that can account for observed dendritic plateau potentials in vivo conditions. In a multicompartmental model neuron with realistic synaptic input, we show that noise-induced bistability persists in a wide range of parameters. Using Fredholm's theory to calculate the spiking rate of multivariable neurons, we discuss how dendritic bistability shifts the spiking dynamics of single neurons and its implications for network phenomena in the processing of in vivo–like fluctuating input.

Self-control is a central aspect of free will. Because self-control is often described in terms of resisting temptations, research on the cognitive neuroscience of free will often focuses on mechanisms of top-down regulation. We argue that this obscures a crucial temporal dimension of free will: now-then regulation. We distinguish now-then regulation from top-down regulation, and situate now-then regulation within a broader account of temporally extended agency. In highlighting this temporal dimension of control, we aim to provide a more nuanced account of how motivation informs action over time, different kinds of regulatory processes underlying the planning and execution of action, and the temporal components of reasons-responsiveness.

In this talk, I’ll introduce the formal concept of a (pre)sheaf as data attached to a topological space. Sheaves capture the notion of patching local sources of information to form a global whole, e.g., the binding of visual features such as colour and shape. The formal theory appears to be closely related to the foundational properties asserted by the Information Integration Theory (IIT) for phenomenology. A comparison is intended to engender discussion on ways that phenomenology may benefit from a sheaf theory, or (more generally) a category theory approach.

Neuroscientific methods successfully account for a system’s functional properties, but leave out the subjective properties of the accompanying experience. According to IIT, phenomenology can be studied scientifically by unfolding the cause-effect structure specified by a system. To illustrate how, in this talk I compare two systems (a grid and a map) to show that they can be functionally equivalent in performing fixation, but only one can specify a cause-effect structure that accounts for the extendedness of phenomenal space.

TBC