Jörn Diedrichsen

We are looking to recruit a new postdoctoral associate for a large collaborative project on the anatomical development of the human cerebellum. The overall goal of the project is to develop a high-resolution normative model of human cerebellar development across the entire life span. The successful candidate will join the Diedrichsen Lab (Western University, Canada) and will work with a team of colleagues at Erasmus Medical Center, the Donders Institute (Netherlands), McGill, Dalhousie, Sick Kids, and UBC (Canada).

Decoding ketamine: Neurobiological mechanisms underlying its rapid antidepressant efficacy

Unlike traditional monoamine-based antidepressants that require weeks to exert effects, ketamine alleviates depression within hours, though its clinical use is limited by side effects. While ketamine was initially thought to work primarily through NMDA receptor (NMDAR) inhibition, our research reveals a more complex mechanism. We demonstrate that NMDAR inhibition alone cannot explain ketamine's sustained antidepressant effects, as other NMDAR antagonists like MK-801 lack similar efficacy. Instead, the (2R,6R)-hydroxynorketamine (HNK) metabolite appears critical, exhibiting antidepressant effects without ketamine's side effects. Paradoxically, our findings suggest an inverted U-shaped dose-response relationship where excessive NMDAR inhibition may actually impede antidepressant efficacy, while some level of NMDAR activation is necessary. The antidepressant actions of ketamine and (2R,6R)-HNK require AMPA receptor activation, leading to synaptic potentiation and upregulation of AMPA receptor subunits GluA1 and GluA2. Furthermore, NMDAR subunit GluN2A appears necessary and possibly sufficient for these effects. This research establishes NMDAR-GluN2A activation as a common downstream effector for rapid-acting antidepressants, regardless of their initial targets, offering promising directions for developing next-generation antidepressants with improved efficacy and reduced side effects.

Imagining and seeing: two faces of prosopagnosia

Feedback-induced dispositional changes in risk preferences

Contrary to the original normative decision-making standpoint, empirical studies have repeatedly reported that risk preferences are affected by the disclosure of choice outcomes (feedback). Although no consensus has yet emerged regarding the properties and mechanisms of this effect, a widespread and intuitive hypothesis is that repeated feedback affects risk preferences by means of a learning effect, which alters the representation of subjective probabilities. Here, we ran a series of seven experiments (N= 538), tailored to decipher the effects of feedback on risk preferences. Our results indicate that the presence of feedback consistently increases risk-taking, even when the risky option is economically less advantageous. Crucially, risk-taking increases just after the instructions, before participants experience any feedback. These results challenge the learning account, and advocate for a dispositional effect, induced by the mere anticipation of feedback information. Epistemic curiosity and regret avoidance may drive this effect in partial and complete feedback conditions, respectively.

There’s more to timing than time: P-centers, beat bins and groove in musical microrhythm

How does the dynamic shape of a sound affect its perceived microtiming? In the TIME project, we studied basic aspects of musical microrhythm, exploring both stimulus features and the participants’ enculturated expertise via perception experiments, observational studies of how musicians produce particular microrhythms, and ethnographic studies of musicians’ descriptions of microrhythm. Collectively, we show that altering the microstructure of a sound (“what” the sound is) changes its perceived temporal location (“when” it occurs). Specifically, there are systematic effects of core acoustic factors (duration, attack) on perceived timing. Microrhythmic features in longer and more complex sounds can also give rise to different perceptions of the same sound. Our results shed light on conflicting results regarding the effect of microtiming on the “grooviness” of a rhythm.

Cognitive Computational Neuroscience 2023

CCN is an annual conference that serves as a forum for cognitive science, neuroscience, and artificial intelligence researchers dedicated to understanding the computations that underlie complex behavior.

Workplace Experiences of LGBTQIA+ Academics in Psychology, Psychiatry, and Neuroscience

In this webinar, Dr David Pagliaccio discusses the findings of his recent pre-print on workplace bias and discrimination faced by LGBTQIA+ brain scientists in the US.

Targeting Maladaptive Emotional Memories to Treat Mental Health Disorders: Insights from Rodent Models

Maladaptive emotional memories contribute to the persistence of numerous mental health disorders, including post-traumatic stress disorder (PTSD), drug addiction and obsessive-compulsive disorder (OCD). Using rodent behavioural models of the psychological processes relevant to these disorders, it is possible to identify potential treatment targets for the development of new therapies, including those based upon disrupting the reconsolidation of maladaptive emotional memories. Using examples from rodent models relevant to multiple mental health disorders, this talk will consider some of the opportunities and challenges that this approach provides.

Spatial matching tasks for insect minds: relational similarity in bumblebees

Understanding what makes human unique is a fundamental research drive for comparative psychologists. Cognitive abilities such as theory of mind, cooperation or mental time travel have been considered uniquely human. Despite empirical evidence showing that animals other than humans are able (to some extent) of these cognitive achievements, findings are still heavily contested. In this context, being able to abstract relations of similarity has also been considered one of the hallmarks of human cognition. While previous research has shown that other animals (e.g., primates) can attend to relational similarity, less is known about what invertebrates can do. In this talk, I will present a series of spatial matching tasks that previously were used with children and great apes and that I adapted for use with wild-caught bumblebees. The findings from these studies suggest striking similarities between vertebrates and invertebrates in their abilities to attend to relational similarity.

Investigating semantics above and beyond language: a clinical and cognitive neuroscience approach

The ability to build, store, and manipulate semantic representations lies at the core of all our (inter)actions. Combining evidence from cognitive neuroimaging and experimental neuropsychology, I study the neurocognitive correlates of semantic knowledge in relation to other cognitive functions, chiefly language. In this talk, I will start by reviewing neuroimaging findings supporting the idea that semantic representations are encoded in distributed yet specialized cortical areas (1), and rapidly recovered (2) according to the requirement of the task at hand (3). I will then focus on studies conducted in neurodegenerative patients, offering a unique window on the key role played by a structurally and functionally heterogeneous piece of cortex: the anterior temporal lobe (4,5). I will present pathological, neuroimaging, cognitive, and behavioral data illustrating how damages to language-related networks can affect or spare semantic knowledge as well as possible paths to functional compensation (6,7). Time permitting, we will discuss the neurocognitive dissociation between nouns and verbs (8) and how verb production is differentially impacted by specific language impairments (9).

Bridging clinical and cognitive neuroscience together to investigate semantics, above and beyond language

We will explore how neuropsychology can be leveraged to directly test cognitive neuroscience theories using the case of frontotemporal dementias affecting the language network. Specifically, we will focus on pathological, neuroimaging, and cognitive data from primary progressive aphasia. We will see how they can help us investigate the reading network, semantic knowledge organisation, and grammatical categories processing. Time permitting, the end of the talk will cover the temporal dynamics of semantic dimensions recovery and the role played by the task.

Curiosity: Some understandings and many challenges

Attention in Psychology, Neuroscience, and Machine Learning

Using eye tracking to investigate neural circuits in health and disease

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.

The neural basis of flexible semantic cognition (BACN Mid-career Prize Lecture 2022)

Semantic cognition brings meaning to our world – it allows us to make sense of what we see and hear, and to produce adaptive thoughts and behaviour. Since we have a wealth of information about any given concept, our store of knowledge is not sufficient for successful semantic cognition; we also need mechanisms that can steer the information that we retrieve so it suits the context or our current goals. This talk traces the neural networks that underpin this flexibility in semantic cognition. It draws on evidence from multiple methods (neuropsychology, neuroimaging, neural stimulation) to show that two interacting heteromodal networks underpin different aspects of flexibility. Regions including anterior temporal cortex and left angular gyrus respond more strongly when semantic retrieval follows highly-related concepts or multiple convergent cues; the multivariate responses in these regions correspond to context-dependent aspects of meaning. A second network centred on left inferior frontal gyrus and left posterior middle temporal gyrus is associated with controlled semantic retrieval, responding more strongly when weak associations are required or there is more competition between concepts. This semantic control network is linked to creativity and also captures context-dependent aspects of meaning; however, this network specifically shows more similar multivariate responses across trials when association strength is weak, reflecting a common controlled retrieval state when more unusual associations are the focus. Evidence from neuropsychology, fMRI and TMS suggests that this semantic control network is distinct from multiple-demand cortex which supports executive control across domains, although challenging semantic tasks recruit both networks. The semantic control network is juxtaposed between regions of default mode network that might be sufficient for the retrieval of strong semantic relationships and multiple-demand regions in the left hemisphere, suggesting that the large-scale organisation of flexible semantic cognition can be understood in terms of cortical gradients that capture systematic functional transitions that are repeated in temporal, parietal and frontal cortex.

Can I be bothered? Neural and computational mechanisms underlying the dynamics of effort processing (BACN Early-career Prize Lecture 2021)

From a workout at the gym to helping a colleague with their work, everyday we make decisions about whether we are willing to exert effort to obtain some sort of benefit. Increases in how effortful actions and cognitive processes are perceived to be has been linked to clinically severe impairments to motivation, such as apathy and fatigue, across many neurological and psychiatric conditions. However, the vast majority of neuroscience research has focused on understanding the benefits for acting, the rewards, and not on the effort required. As a result, the computational and neural mechanisms underlying how effort is processed are poorly understood. How do we compute how effortful we perceive a task to be? How does this feed into our motivation and decisions of whether to act? How are such computations implemented in the brain? and how do they change in different environments? I will present a series of studies examining these questions using novel behavioural tasks, computational modelling, fMRI, pharmacological manipulations, and testing in a range of different populations. These studies highlight how the brain represents the costs of exerting effort, and the dynamic processes underlying how our sensitivity to effort changes as a function of our goals, traits, and socio-cognitive processes. This work provides new computational frameworks for understanding and examining impaired motivation across psychiatric and neurological conditions, as well as why all of us, sometimes, can’t be bothered.

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.

Mapping Individual Trajectories of Structural and Cognitive Decline in Mild Cognitive Impairment

The US has an aging population. For the first time in US history, the number of older adults is projected to outnumber that of children by 2034. This combined with the fact that the prevalence of Alzheimer's Disease increases exponentially with age makes for a worrying combination. Mild cognitive impairment (MCI) is an intermediate stage of cognitive decline between being cognitively normal and having full-blown Dementia, with every third person with MCI progressing to dementia of the Alzheimer's Type (DAT). While there is no known way to reverse symptoms once they begin, early prediction of disease can help stall its progression and help with early financial planning. While grey matter volume loss in the Hippocampus and Entorhinal Cortex (EC) are characteristic biomarkers of DAT, little is known about the rates of decrease of these volumes within individuals in MCI state across time. We used longitudinal growth curve models to map individual trajectories of volume loss in subjects with MCI. We then looked at whether these rates of volume decrease could predict progression to DAT right in the MCI stage. Finally, we evaluated whether these rates of Hippocampal and EC volume loss were correlated with individual rates of decline of episodic memory, visuospatial ability, and executive function.

Biopsychosocial pathways in dementia inequalities

In the United States, racial/ethnic inequalities in Alzheimer's disease and related dementias persist even after controlling for socioeconomic factors and physical health. These persistent and unexplained disparities suggest: (1) there are unrecognized dementia risk factors that are socially patterned and/or (2) known dementia risk factors exhibit differential impact across social groups. Pursuing these research directions with data from multiple longitudinal studies of brain and cognitive aging has revealed several challenges to the study of late-life health inequalities, highlighted evidence for both risk and resilience within marginalized communities, and inspired new data collection efforts to advance the field.

The neuroscience of lifestyle interventions for mental health: the BrainPark approach

Our everyday behaviours, such as physical activity, sleep, diet, meditation, and social connections, have a potent impact on our mental health and the health of our brain. BrainPark is working to harness this power by developing lifestyle-based interventions for mental health and investigating how they do and don’t change the brain, and for whom they are most effective. In this webinar, Dr Rebecca Segrave and Dr Chao Suo will discuss BrainPark’s approach to developing lifestyle-based interventions to help people get better control of compulsive behaviours, and the multi-modality neuroimaging approaches they take to investigating outcomes. The webinar will explore two current BrainPark trials: 1. Conquering Compulsions - investigating the capacity of physical exercise and meditation to alter reward processing and help people get better control of a wide range of unhelpful habits, from drinking to eating to cleaning. 2. The Brain Exercise Addiction Trial (BEAT) - an NHMRC funded investigation into the capacity of physical exercise to reverse the brain harms caused by long-term heavy cannabis use. Dr Rebecca Segrave is Deputy Director and Head of Interventions Research at BrainPark, the David Winston Turner Senior Research Fellow within the Turner Institute for Brain and Mental Health, and an AHRPA registered Clinical Neuropsychologist. Dr Chao Suo is Head of Technology and Neuroimaging at BrainPark and a Research Fellow within the Turner Institute for Brain and Mental Health.

Growing Up in Academia with Onur Güntürkün

There are stories of resilience, passion, braveness and determination and the one of Onur Güntürkün. He has managed to beat the odds in so many ways, from moving countries, surviving the polio, establishing a new field against the advice of a senior professor and much more, all the while keeping a positive spirit, an endless curiosity and the braveness to keep going despite adversities. Join me on Monday, February 28, 2022, 6 p.m. (CET) for a Growing Up in Academia with Onur Güntürkün.

What is Cognitive Neuropsychology Good For? An Unauthorized Biography

Abstract: There is no doubt that the study of brain damaged individuals has contributed greatly to our understanding of the mind/brain. Within this broad approach, cognitive neuropsychology accentuates the cognitive dimension: it investigates the structure and organization of perceptual, motor, cognitive, and language systems – prerequisites for understanding the functional organization of the brain – through the analysis of their dysfunction following brain damage. Significant insights have come specifically from this paradigm. But progress has been slow and enthusiasm for this approach has waned somewhat in recent years, and the use of existing findings to constrain new theories has also waned. What explains the current diminished status of cognitive neuropsychology? One reason may be failure to calibrate expectations about the effective contribution of different subfields of the study of the mind/brain as these are determined by their natural peculiarities – such factors as the types of available observations and their complexity, opportunity of access to such observations, the possibility of controlled experimentation, and the like. Here, I also explore the merits and limitations of cognitive neuropsychology, with particular focus on the role of intellectual, pragmatic, and societal factors that determine scientific practice within the broader domains of cognitive science/neuroscience. I conclude on an optimistic note about the continuing unique importance of cognitive neuropsychology: although limited to the study of experiments of nature, it offers a privileged window into significant aspects of the mind/brain that are not easily accessible through other approaches. Biography: Alfonso Caramazza's research has focussed extensively on how words and their meanings are represented in the brain. His early pioneering studies helped to reformulate our thinking about Broca's aphasia (not limited to production) and formalised the logic of patient-based neuropsychology. More recently he has been instrumental in reconsidering popular claims about embodied cognition.

Reasoning Ability: Neural Mechanisms, Development, and Plasticity

Relational thinking, or the process of identifying and integrating relations between mental representations, is regularly invoked during reasoning. This mental capacity enables us to draw higher-order abstractions and generalize across situations and contexts, and we have argued that it should be included in the pantheon of executive functions. In this talk, I will briefly review our lab's work characterizing the roles of lateral prefrontal and parietal regions in relational thinking. I will then discuss structural and functional predictors of individual differences and developmental changes in reasoning.

Architectural Psychology with Professor David Canter

Emotions are constructed of more basic networks

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.

How bilingualism modulates the neural mechanisms of selective attention

Learning and using multiple languages places considerable demands on our cognitive system, and has been shown to modulate the mechanisms of selective attention in both children and adults. Yet the nature of these adaptive changes is still not entirely clear. One possibility is that bilingualism boosts the capacity for selective attention; another is that it leads to a different distribution of this finite resource, aimed at supporting optimal performance under the increased processing demands. I will present a series of studies investigating the nature of modifications of selective attention in bilingualism. Using behavioural and neuroimaging techniques, our data confirm that bilingualism modifies the neural mechanisms of selective attention even in the absence of behavioural differences between monolinguals and bilinguals. They further suggest that, instead of enhanced attentional capacity, these neuroadaptive modifications appear to reflect its redistribution, arguably aimed at economising the available resources to support optimal behavioural performance.

The pervasive role of visuospatial coding

Historically, retinotopic organisation (the spatial mapping of the retina across the cortical surface) was considered the purview of early regions of visual cortex (V1-V4) only and that anterior, more cognitively involved regions abstracted this information away. The contemporary view is quite different. Here, with Advancing technologies and analysis methods, we see that retinotopic information is not simply thrown away by these regions but rather is maintained to the potential benefit of our broader cognition. This maintenance of visuospatial coding extends not only through visual cortex, but is present in parietal, frontal, medial and subcortical structures involved with coordinating-movements, mind-wandering and even memory. In this talk, I will outline some of the key empirical findings from my own work and the work of others that shaped this contemporary perspective.

Towards an inclusive neurobiology of language

Understanding how our brains process language is one of the fundamental issues in cognitive science. In order to reach such understanding, it is critical to cover the full spectrum of manners in which humans acquire and experience language. However, due to a myriad of socioeconomic factors, research has disproportionately focused on monolingual English speakers. In this talk, I present a series of studies that systematically target fundamental questions about bilingual language use across a range of conversational contexts, both in production and comprehension. The results lay the groundwork to propose a more inclusive theory of the neurobiology of language, with an architecture that assumes a common selection principle at each linguistic level and can account for attested features of both bilingual and monolingual speech in, but crucially also out of, experimental settings.

Limbic generators of delight, desire and dread

Scaffolding up from Social Interactions: A proposal of how social interactions might shape learning across development

Social learning and analogical reasoning both provide exponential opportunities for learning. These skills have largely been studied independently, but my future research asks how combining skills across previously independent domains could add up to more than the sum of their parts. Analogical reasoning allows individuals to transfer learning between contexts and opens up infinite opportunities for innovation and knowledge creation. Its origins and development, so far, have largely been studied in purely cognitive domains. Constraining analogical development to non-social domains may mistakenly lead researchers to overlook its early roots and limit ideas about its potential scope. Building a bridge between social learning and analogy could facilitate identification of the origins of analogical reasoning and broaden its far-reaching potential. In this talk, I propose that the early emergence of social learning, its saliency, and its meaningful context for young children provides a springboard for learning. In addition to providing a strong foundation for early analogical reasoning, the social domain provides an avenue for scaling up analogies in order to learn to learn from others via increasingly complex and broad routes.

Understanding the Assessment of Spatial Neglect and its Treatment Using Prism Adaptation Training

Spatial neglect is a syndrome that is most frequently associated with damage to the right hemisphere, although damage to the left hemisphere can also result in signs of spatial neglect. It is characterised by absent or deficient awareness of the contralesional side of space. The screening and diagnosis of spatial neglect lacks a universal gold standard, but is usually achieved by using various modes of assessment. Spatial neglect is also difficult to treat, although prism adaptation training (PAT) has in the past reportedly showed some promise. This seminar will include highlights from a series of studies designed to identify knowledge gaps, and will suggest ways in which these can be bridged. The first study was conducted to identify and quantify clinicians’ use of assessment tools for spatial neglect, finding that several different tools are in use, but that there is an emerging consensus and appetite for harmonisation. The second study included PAT, and sought to uncover whether PAT can improve engagement in recommended therapy in order to improve the outcomes of stroke survivors with spatial neglect. The final study, a systematic review and meta-analysis, sought to investigate the scientific efficacy (rather than clinical effectiveness) of PAT, identifying several knowledge gaps in the existing literature and a need for a new approach in the study of PAT in the clinical setting.

Strong and weak principles of neural dimension reduction

Large-scale, single neuron resolution recordings are inherently high-dimensional, with as many dimensions as neurons. To make sense of them, for many the answer is: reduce the number of dimensions. In this talk I argue we can distinguish weak and strong principles of neural dimension reduction. The weak principle is that dimension reduction is a convenient tool for making sense of complex neural data. The strong principle is that dimension reduction moves us closer to how neural circuits actually operate and compute. Elucidating these principles is crucial, for which we subscribe to provides radically different interpretations of the same dimension reduction techniques applied to the same data. I outline experimental evidence for each principle, but illustrate how we could make either the weak or strong principles appear to be true based on innocuous looking analysis decisions. These insights suggest arguments over low and high-dimensional neural activity need better constraints from both experiment and theory.

Sleep and Plasticity - New insights from in vivo calcium imaging

Neural stem cells as biomarkers of cognitive aging and dementia

Adult hippocampal neurogenesis is implicated in memory formation and mood regulation. The Thuret lab investigates environmental and molecular mechanisms controlling the production of these adult-born neurons and how they impact mental health. We study neurogenesis in healthy ageing as well as in the context of diseases such as Alzheimer’s and depression. By approaching neurogenesis in health and disease, the strategy is two folds: (i) Validating the neurogenic process as a target for prevention and pharmacological interventions. (ii) Developing neurogenesis as a biomarker of disease prediction and progression. In this talk, I will focus on presenting some recent human studies demonstrating how hippocampal neural stem cells fate can be used as biomarkers of cognitive aging and dementia.

A reward-learning framework of knowledge acquisition

Recent years have seen a considerable surge of research on interest-based engagement, examining how and why people are engaged in activities without relying on extrinsic rewards. However, the field of inquiry has been somewhat segregated into three different research traditions which have been developed relatively independently --- research on curiosity, interest, and trait curiosity/interest. The current talk sets out an integrative perspective; the reward-learning framework of knowledge acquisition. This conceptual framework takes on the basic premise of existing reward-learning models of information seeking: that knowledge acquisition serves as an inherent reward, which reinforces people’s information-seeking behavior through a reward-learning process. However, the framework reveals how the knowledge-acquisition process is sustained and boosted over a long period of time in real-life settings, allowing us to integrate the different research traditions within reward-learning models. The framework also characterizes the knowledge-acquisition process with four distinct features that are not present in the reward-learning process with extrinsic rewards --- (1) cumulativeness, (2) selectivity, (3) vulnerability, and (4) under-appreciation. The talk describes some evidence from our lab supporting these claims.

Exploring the interplay of glucocorticoids, daily timing, sleep, and psychology-based task performance

FENS Forum 2024

Identifying central timing mechanisms in the human cerebellum across explicit and implicit timing: A combined neuropsychology-electroencephalography approach

FENS Forum 2024