The PhD in Medical Sciences: The University of Nicosia Medical School offers the degree PhD in Medical Sciences. The degree is awarded to students who successfully complete an independent research programme that breaks new ground in the chosen field of study. The PhD programme aspires to empower students to become independent researchers, thus advancing innovation and development. The Research Project: We are currently inviting application through a competitive process for high calibre candidates to apply for one PhD Scholarship in the field of Neuroscience. The successful candidate will enrol on the PhD programme in Medical Sciences and will work under the Supervision of Prof Avgis Hadjipapas, Professor for Neuroscience and Research Methods at the University of Nicosia Medical School. The project is based on an international collaboration between the University of Nicosia Medical School, (UN) the University Maastricht University Medical Center (MUMC), Maastricht University (MU) and McGill University (McGill U). The project predominantly involves data-analysis (signal processing), which means that a large part of the project can be conducted remotely. Project Description: Title of research project: Characterization of circadian rhythm modulations in intracranial EEG and their relationship to seizure onsets in focal epilepsy Background, rationale and objectives: Epilepsy affects roughly 1% of the population, and about a third of patients have unpredictable seizures which cannot be adequately controlled with medication (Kuhlmann et al., 2018). Therefore, better understanding of seizure generation and improving seizure predictability are central goals in epilepsy research to prevent seizures from occurring. Recent investigations by our own (Mitsis et al., 2020) and other groups (Leguia et al., 2021) have shown that seizure onsets exhibit a tight correlation to certain phases of circadian rhythms, which leads to improved seizure predictability. However, our previous work (Mitsis et al., 2020) only utilized surface EEG. In this project, and based on a collaboration formed between the University of Nicosia Medical School (UN), Maastricht University Medical Center (MUMC), Maastricht University (MU), and McGill University (McGill U), we will address this question by examining intracranial recordings provided by the MUMC partner, obtained directly from the area of the suspected epileptogenic focus. We will first characterize in detail the circadian variation of signal parameters extracted from the intracranial EEG. We will then examine whether seizure onsets are phase coupled (correlated) to these circadian modulations. This will inform both important pathophysiological questions in terms of the extent of the functional seizure generating network. Further, analysis of this correlation at the level of individual patient recordings will inform the feasibility of seizure forecasting informed by circadian rhythms. Successful candidates will benefit from interacting with an international and interdisciplinary consortium of neuroscientists, neurologists and engineers throughout the duration of the project. References Karoly, P.J., Ung, H., Grayden, D.B., Kuhlmann, L., Leyde, K., Cook, M.J., Freestone, D.R., 2017. The circadian profile of epilepsy improves seizure forecasting. Brain 140, 2169–2182. https://doi.org/10.1093/brain/awx173 Kuhlmann, L., Lehnertz, K., Richardson, M.P., Schelter, B., Zaveri, H.P., 2018. Seizure prediction — ready for a new era. Nat. Rev. Neurol. https://doi.org/10.1038/s41582-018-0055-2 Leguia, M.G., Andrzejak, R.G., Rummel, C., Fan, J.M., Mirro, E.A., Tcheng, T.K., Rao, V.R., Baud, M.O., 2021. Seizure Cycles in Focal Epilepsy. JAMA Neurol. In press, 1–10. https://doi.org/10.1001/jamaneurol.2020.5370 Mitsis, G.D., Anastasiadou, M.N., Christodoulakis, M., Papathanasiou, E.S., Papacostas, S.S., Hadjipapas, A., 2020. Functional brain networks of patients with epilepsy exhibit pronounced multiscale periodicities, which correlate with seizure onset. Hum. Brain Mapp. hbm.24930. https://doi.org/10.1002/hbm.24930 The Scholarship: The Scholarship will have a duration of three to four years and will cover: • The tuition fees for the PhD programme which are €13,500 in total for the first 3 years and €1,500 for year 4. • A monthly stipend of €1,000 for the duration of three to four years. Application for the PhD Scholarship: Candidates should submit an online application through this link and upload the following supporting documents: • A cover letter clearly stating that they apply for the PhD Scholarship in the field of Neuroscience for the PhD Research Project ‘Characterization of circadian rhythm modulations in intracranial EEG and their relationship to seizure onsets in focal epilepsy.’ • Copies of the applicant’s qualifications/degree(s) – the application can be assessed with scanned copies, but certified true copies must be provided if the candidate is successful and prior to enrolment on the PhD programme. • Copies of the applicant’s transcript(s) - the application can be assessed with scanned copies, but certified true copies must be provided if the candidate is successful and prior to enrolment on the PhD programme. • Proof of English language proficiency such as IELTS with a score of 7 overall and with a minimum score of 7 in writing or TOEFL iBT with a score of 94 overall and a minimum score of 27 in Writing. Other internationally recognized English language qualifications might be considered upon review. Students from the UK, Ireland USA, Canada (from English speaking provinces), Australia and New Zealand are exempt from the English language requirement. • Two reference letters, of which at least one should be from an academic. • A full Curriculum Vitae (CV). Applications should be submitted by Friday, July 29, 2022 at 5pm. Only fully completed applications, containing all necessary supporting documents will be reviewed. Only candidates who are shortlisted will be contacted and invited to an interview.

The post-doc/PhD will be fully dedicated to extracting the EEG correlates of rhythm processing in the course of development, aiming to extract the neural response to different rhythmic characteristics, and to evaluate the impact of musical interventions on neurodevelopment. The project aims to evaluate the development of rhythm perception starting from the third trimester of gestation into infancy, and the impact of early musical interventions in the NICU on preterm infants’ development. In this cross-sectional and longitudinal study, we will evaluate the development of auditory rhythm processing capacities with EEG, and behavioral protocols.

A postdoc position is available under the shared supervision of Prof. Maxime Baud and Dr. Timothée Proix, who both specialize in quantitative neuroscience research. Together, they are running a three-year clinical trial involving patients with epilepsy who received a minimally invasive EEG device beneath the scalp for the chronic recording (months) of brain signals during wake and sleep. The postdoc will help with the analysis of massive amounts of EEG data, with a desire to build forecasting algorithms aiming at estimating the risk of seizures 24 hours in advance. The project lies at the interface between machine learning and EEG data analysis. The goal of the project is to develop machine learning algorithms to forecast seizures.

We have an opening for a postdoc position investigating the neural bases of deep multimodal learning in the brain. The project involves EEG and laminar 7T imaging (in collaboration with Dr. Peter Bandettini’s lab at NIMH) to test computational hypotheses for how the brain learns multimodal concept representations. Responsibilities of the postdoc include running EEG and fMRI experiments, data analysis and manuscript preparation. Georgetown University has a vibrant neuroscience community with over fifty labs participating in the Interdisciplinary Program in Neuroscience and a number of relevant research centers, including the new Center for Neuroengineering (cne.georgetown.edu). Interested candidates should submit a CV, a brief (1 page) statement of research interests, representative reprints, and the names and contact information of three references to Interfolio via https://apply.interfolio.com/148520. Faxed, emailed, or mailed applications will not be accepted. Questions about the position can be directed to Maximilian Riesenhuber (mr287@georgetown.edu).

Mentalab, a German company developing mobile EEG systems, is seeking a talented neuroscientist to join our growing sales team. This is a great opportunity for someone passionate about innovative technology and eager to contribute to the wider field of EEG.

Traditionally, touch is associated with exteroception and is rarely considered a relevant sensory cue for controlling movements in space, unlike vision. We developed a technique to isolate and measure tactile involvement in controlling sliding finger movements over a surface. Young adults traced a 2D shape with their index finger under direct or mirror-reversed visual feedback to create a conflict between visual and somatosensory inputs. In this context, increased reliance on somatosensory input compromises movement accuracy. Based on the hypothesis that tactile cues contribute to guiding hand movements when in contact with a surface, we predicted poorer performance when the participants traced with their bare finger compared to when their tactile sensation was dampened by a smooth, rigid finger splint. The results supported this prediction. EEG source analyses revealed smaller current in the source-localized somatosensory cortex during sensory conflict when the finger directly touched the surface. This finding supports the hypothesis that, in response to mirror-reversed visual feedback, the central nervous system selectively gated task-irrelevant somatosensory inputs, thereby mitigating, though not entirely resolving, the visuo-somatosensory conflict. Together, our results emphasize touch’s involvement in movement control over a surface, challenging the notion that vision predominantly governs goal-directed hand or finger movements.

Electroencephalography (EEG) has been thoroughly studied for decades in psychiatry research. Yet its integration into clinical practice as a diagnostic/prognostic tool remains unachieved. We hypothesize that a key reason is the underlying patient's heterogeneity, overlooked in psychiatric EEG research relying on a case-control approach. We combine HD-EEG with normative modeling to quantify this heterogeneity using two well-established and extensively investigated EEG characteristics -spectral power and functional connectivity- across a cohort of 1674 patients with attention-deficit/hyperactivity disorder, autism spectrum disorder, learning disorder, or anxiety, and 560 matched controls. Normative models showed that deviations from population norms among patients were highly heterogeneous and frequency-dependent. Deviation spatial overlap across patients did not exceed 40% and 24% for spectral and connectivity, respectively. Considering individual deviations in patients has significantly enhanced comparative analysis, and the identification of patient-specific markers has demonstrated a correlation with clinical assessments, representing a crucial step towards attaining precision psychiatry through EEG.

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.

Comprehending speech under acoustically challenging conditions is an everyday task that we can often execute with ease. However, accomplishing this requires the engagement of cognitive resources, such as auditory attention and working memory. The mechanisms that contribute to the robustness of speech comprehension are of substantial interest in the context of hearing mild to moderate hearing impairment, in which affected individuals typically report specific difficulties in understanding speech in background noise. Although hearing aids can help to mitigate this, they do not represent a universal solution, thus, finding alternative interventions is necessary. Given that age-related hearing loss (“presbycusis”) is inevitable, developing new approaches is all the more important in the context of aging populations. Moreover, untreated hearing loss in middle age has been identified as the most significant potentially modifiable predictor of dementia in later life. I will present research that has used a multi-methodological approach (fMRI, EEG, MEG and non-invasive brain stimulation) to try to elucidate the mechanisms that comprise the cognitive “last mile” in speech acousticallychallenging speech comprehension and to find ways to enhance them.

Neural entrainment has become a phenomenon of exceptional interest to neuroscience, given its involvement in rhythm perception, production, and overt synchronized behavior. Yet, traditional methods fail to quantify neural entrainment due to a misalignment with its fundamental definition (e.g., see Novembre and Iannetti, 2018; Rajandran and Schupp, 2019). The definition of entrainment assumes that endogenous oscillatory brain activity undergoes dynamic frequency adjustments to synchronize with environmental rhythms (Lakatos et al., 2019). Following this definition, we recently developed a method sensitive to this process. Our aim was to isolate from the electroencephalographic (EEG) signal an oscillatory component that is attuned to the frequency of a rhythmic stimulation, hypothesizing that the oscillation would adaptively speed up and slow down to achieve stable synchronization over time. To induce and measure these adaptive changes in a controlled fashion, we developed the event-related frequency adjustment (ERFA) paradigm (Rosso et al., 2023). A total of twenty healthy participants took part in our study. They were instructed to tap their finger synchronously with an isochronous auditory metronome, which was unpredictably perturbed by phase-shifts and tempo-changes in both positive and negative directions across different experimental conditions. EEG was recorded during the task, and ERFA responses were quantified as changes in instantaneous frequency of the entrained component. Our results indicate that ERFAs track the stimulus dynamics in accordance with the perturbation type and direction, preferentially for a sensorimotor component. The clear and consistent patterns confirm that our method is sensitive to the process of frequency adjustment that defines neural entrainment. In this Virtual Journal Club, the discussion of our findings will be complemented by methodological insights beneficial to researchers in the fields of rhythm perception and production, as well as timing in general. We discuss the dos and don’ts of using instantaneous frequency to quantify oscillatory dynamics, the advantages of adopting a multivariate approach to source separation, the robustness against the confounder of responses evoked by periodic stimulation, and provide an overview of domains and concrete examples where the methodological framework can be applied.

The human voice is possibly the most important sound category in the social landscape. Compared to other non-verbal emotion signals, the voice is particularly effective in communicating emotions: it can carry information over large distances and independent of sight. However, the study of vocal emotion expression and perception is surprisingly far less developed than the study of emotion in faces. Thereby, its neural and functional correlates remain elusive. As the voice represents a dynamically changing auditory stimulus, temporally sensitive techniques such as the EEG are particularly informative. In this talk, the dynamic neurocognitive operations that take place when we listen to vocal emotions will be specified, with a focus on the effects of stimulus type, task demands, and speaker and listener characteristics (e.g., age). These studies suggest that emotional voice perception is not only a matter of how one speaks but also of who speaks and who listens. Implications of these findings for the understanding of psychiatric disorders such as schizophrenia will be discussed.

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.

Sleep strongly affects synaptic strength, making it critical for cognition, especially learning and memory formation. Whether and how sleep deprivation modulates human brain physiology and cognition is poorly understood. Here we examined how overnight sleep deprivation vs overnight sufficient sleep affects (a) cortical excitability, measured by transcranial magnetic stimulation, (b) inducibility of long-term potentiation (LTP)- and long-term depression (LTD)-like plasticity via transcranial direct current stimulation (tDCS), and (c) learning, memory, and attention. We found that sleep deprivation increases cortical excitability due to enhanced glutamate-related cortical facilitation and decreases and/or reverses GABAergic cortical inhibition. Furthermore, tDCS-induced LTP-like plasticity (anodal) abolishes while the inhibitory LTD-like plasticity (cathodal) converts to excitatory LTP-like plasticity under sleep deprivation. This is associated with increased EEG theta oscillations due to sleep pressure. Motor learning, behavioral counterparts of plasticity, and working memory and attention, which rely on cortical excitability, are also impaired during sleep deprivation. Our study indicates that upscaled brain excitability and altered plasticity, due to sleep deprivation, are associated with impaired cognitive performance. Besides showing how brain physiology and cognition undergo changes (from neurophysiology to higher-order cognition) under sleep pressure, the findings have implications for variability and optimal application of noninvasive brain stimulation.

Advanced noninvasive neuroimaging methods provide valuable information on the brain function, but they have obvious pros and cons in terms of temporal and spatial resolution. Functional magnetic resonance imaging (fMRI) using blood-oxygenation-level-dependent (BOLD) effect provides good spatial resolution in the order of millimeters, but has a poor temporal resolution in the order of seconds due to slow hemodynamic responses to neuronal activation, providing indirect information on neuronal activity. In contrast, electroencephalography (EEG) and magnetoencephalography (MEG) provide excellent temporal resolution in the millisecond range, but spatial information is limited to centimeter scales. Therefore, there has been a longstanding demand for noninvasive brain imaging methods capable of detecting neuronal activity at both high temporal and spatial resolution. In this talk, I will introduce a novel approach that enables Direct Imaging of Neuronal Activity (DIANA) using MRI that can dynamically image neuronal spiking activity in milliseconds precision, achieved by data acquisition scheme of rapid 2D line scan synchronized with periodically applied functional stimuli. DIANA was demonstrated through in vivo mouse brain imaging on a 9.4T animal scanner during electrical whisker-pad stimulation. DIANA with milliseconds temporal resolution had high correlations with neuronal spike activities, which could also be applied in capturing the sequential propagation of neuronal activity along the thalamocortical pathway of brain networks. In terms of the contrast mechanism, DIANA was almost unaffected by hemodynamic responses, but was subject to changes in membrane potential-associated tissue relaxation times such as T2 relaxation time. DIANA is expected to break new ground in brain science by providing an in-depth understanding of the hierarchical functional organization of the brain, including the spatiotemporal dynamics of neural networks.

Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) share similarities in pathology and clinical presentation and come under the umbrella term of Lewy body dementias (LBD). Fluctuating cognition is a key symptom in LBD and manifests as altered levels of alertness and attention, with a marked difference between best and worst performance. Cognition and alertness can change over seconds or minutes to hours and days of obtundation. Cognitive fluctuations can have significant impacts on the quality of life of people with LBD as well as potentially contribute to the exacerbation of other transient symptoms including, for example, hallucinations and psychosis as well as making it difficult to measure cognitive effect size benefits in clinical trials of LBD. However, this significant symptom in LBD is poorly understood. In my presentation I will discuss the phenomenology of cognitive fluctuations, how we can measure it clinically and limitations of these approaches. I will then outline the work of our group and others which has been focussed on unpicking the aetiological basis of cognitive fluctuations in LBD using a variety of imaging approaches (e.g. SPECT, sMRI, fMRI and EEG). I will then briefly explore future research directions.

The ability to organise one's body for action without having to think about it is taken for granted, whether it is handwriting, typing on a smartphone or computer keyboard, tying a shoelace or playing the piano. When compromised, e.g. in stroke, neurodegenerative and developmental disorders, the individuals’ study, work and day-to-day living are impacted with high societal costs. Until recently, indirect methods such as invasive recordings in animal models, computer simulations, and behavioural markers during sequence execution have been used to study covert motor sequence planning in humans. In this talk, I will demonstrate how multivariate pattern analyses of non-invasive neurophysiological recordings (MEG/EEG), fMRI, and muscular recordings, combined with a new behavioural paradigm, can help us investigate the structure and dynamics of motor sequence control before and after movement execution. Across paradigms, participants learned to retrieve and produce sequences of finger presses from long-term memory. Our findings suggest that sequence planning involves parallel pre-ordering of serial elements of the upcoming sequence, rather than a preparation of a serial trajectory of activation states. Additionally, we observed that the human neocortex automatically reorganizes the order and timing of well-trained movement sequences retrieved from memory into lower and higher-level representations on a trial-by-trial basis. This echoes behavioural transfer across task contexts and flexibility in the final hundreds of milliseconds before movement execution. These findings strongly support a hierarchical and dynamic model of skilled sequence control across the peri-movement phase, which may have implications for clinical interventions.

Mobile organisms must be capable of deciding both where and when to move in order to keep up with a changing environment; therefore, a strong sense of time is necessary, otherwise, we would fail in many of our movement goals. Despite this intrinsic link between movement and timing, only recently has research begun to investigate the interaction. Two primary effects that have been observed include: movements biasing time estimates (i.e., affecting accuracy) as well as making time estimates more precise. The goal of this presentation is to review this literature, discuss a Bayesian cue combination framework to explain these effects, and discuss the experiments I have conducted to test the framework. The experiments herein include: a motor timing task comparing the effects of movement vs non-movement with and without feedback (Exp. 1A & 1B), a transcranial magnetic stimulation (TMS) study on the role of the supplementary motor area (SMA) in transforming temporal information (Exp. 2), and a perceptual timing task investigating the effect of noisy movement on time perception with both visual and auditory modalities (Exp. 3A & 3B). Together, the results of these studies support the Bayesian cue combination framework, in that: movement improves the precision of time perception not only in perceptual timing tasks but also motor timing tasks (Exp. 1A & 1B), stimulating the SMA appears to disrupt the transformation of temporal information (Exp. 2), and when movement becomes unreliable or noisy there is no longer an improvement in precision of time perception (Exp. 3A & 3B). Although there is support for the proposed framework, more studies (i.e., fMRI, TMS, EEG, etc.) need to be conducted in order to better understand where and how this may be instantiated in the brain; however, this work provides a starting point to better understanding the intrinsic connection between time and movement

When listening to music, humans readily perceive and move along with a periodic beat. Critically, perception of a periodic beat is commonly elicited by rhythmic stimuli with physical features arranged in a way that is not strictly periodic. Hence, beat perception must capitalize on mechanisms that transform stimulus features into a temporally recurrent format with emphasized beat periodicity. Here, I will present a line of work that aims to clarify the nature and neural basis of this transformation. In these studies, electrophysiological activity was recorded as participants listened to rhythms known to induce perception of a consistent beat across healthy Western adults. The results show that the human brain selectively emphasizes beat representation when it is not acoustically prominent in the stimulus, and this transformation (i) can be captured non-invasively using surface EEG in adult participants, (ii) is already in place in 5- to 6-month-old infants, and (iii) cannot be fully explained by subcortical auditory nonlinearities. Moreover, as revealed by human intracerebral recordings, a prominent beat representation emerges already in the primary auditory cortex. Finally, electrophysiological recordings from the auditory cortex of a rhesus monkey show a significant enhancement of beat periodicities in this area, similar to humans. Taken together, these findings indicate an early, general auditory cortical stage of processing by which rhythmic inputs are rendered more temporally recurrent than they are in reality. Already present in non-human primates and human infants, this "periodized" default format could then be shaped by higher-level associative sensory-motor areas and guide movement in individuals with strongly coupled auditory and motor systems. Together, this highlights the multiplicity of neural processes supporting coordinated musical behaviors widely observed across human cultures.The experiments herein include: a motor timing task comparing the effects of movement vs non-movement with and without feedback (Exp. 1A & 1B), a transcranial magnetic stimulation (TMS) study on the role of the supplementary motor area (SMA) in transforming temporal information (Exp. 2), and a perceptual timing task investigating the effect of noisy movement on time perception with both visual and auditory modalities (Exp. 3A & 3B). Together, the results of these studies support the Bayesian cue combination framework, in that: movement improves the precision of time perception not only in perceptual timing tasks but also motor timing tasks (Exp. 1A & 1B), stimulating the SMA appears to disrupt the transformation of temporal information (Exp. 2), and when movement becomes unreliable or noisy there is no longer an improvement in precision of time perception (Exp. 3A & 3B). Although there is support for the proposed framework, more studies (i.e., fMRI, TMS, EEG, etc.) need to be conducted in order to better understand where and how this may be instantiated in the brain; however, this work provides a starting point to better understanding the intrinsic connection between time and movement

Repetitive spatiotemporal patterns in resting-state brain activities have been widely observed in various species and regions, such as rat and cat visual cortices. Since they resemble the preceding brain activities during tasks, they are assumed to reflect past experiences embedded in neuronal circuits. Moreover, spatiotemporal patterns involving whole-brain activities may also reflect a process that integrates information distributed over the entire brain, such as motor and visual information. Therefore, revealing such patterns may elucidate how the information is integrated to generate consciousness. In this talk, I will introduce our proposed method to estimate repetitive spatiotemporal patterns from resting-state brain activity data and show the spatiotemporal patterns estimated from human resting-state magnetoencephalography (MEG) and electroencephalography (EEG) data. Our analyses suggest that the patterns involved whole-brain propagating activities that reflected a process to integrate the information distributed over frequencies and networks. I will also introduce our current attempt to reveal signal flows and their roles in the spatiotemporal patterns using a big dataset. - Takeda et al., Estimating repetitive spatiotemporal patterns from resting-state brain activity data. NeuroImage (2016); 133:251-65. - Takeda et al., Whole-brain propagating patterns in human resting-state brain activities. NeuroImage (2021); 245:118711.

In most brains across the animal kingdom, brain dynamics can enter pathological states that are recognisable as epileptic seizures. Yet usually, brain operate within certain constraints given through neuronal function and synaptic coupling, that will prevent epileptic seizure dynamics from emerging. In this talk, I will bring together different approaches to identifying how networks in the broadest sense shape brain dynamics. Using illustrative examples from intracranial EEG recordings, disorders characterised by molecular disruption of a single neurotransmitter receptor type, to single-cell recordings of whole-brain activity in the larval zebrafish, I will address three key questions - (1) how does the regionally specific composition of synaptic receptors shape ongoing physiological brain activity; (2) how can disruption of this regionally specific balance result in abnormal brain dynamics; and (3) which cellular patterns underly the transition into an epileptic seizure.

Since Darwin, comparative research has shown that most animals share basic timing capacities, such as the ability to process temporal regularities and produce rhythmic behaviors. What seems to be more exclusive, however, are the capacities to generate temporal predictions and to display anticipatory behavior at salient time points. These abilities are associated with subcortical structures like basal ganglia (BG) and cerebellum (CE), which are more developed in humans as compared to nonhuman animals. In the first research line, we investigated the basic capacities to extract temporal regularities from the acoustic environment and produce temporal predictions. We did so by adopting a comparative and translational approach, thus making use of a unique EEG dataset including 2 macaque monkeys, 20 healthy young, 11 healthy old participants and 22 stroke patients, 11 with focal lesions in the BG and 11 in the CE. In the second research line, we holistically explore the functional relevance of body-brain physiological interactions in human behavior. Thus, a series of planned studies investigate the functional mechanisms by which body signals (e.g., respiratory and cardiac rhythms) interact with and modulate neurocognitive functions from rest and sleep states to action and perception. This project supports the effort towards individual profiling: are individuals’ timing capacities (e.g., rhythm perception and production), and general behavior (e.g., individual walking and speaking rates) influenced / shaped by body-brain interactions?

Following the seminal structure mapping theory by Dedre Gentner, the process of mapping the corresponding structures of relations defining two analogs has been understood as a key component of analogy making. However, not without a merit, in recent years some semantic, pragmatic, and perceptual aspects of analogy mapping attracted primary attention of analogy researchers. For almost a decade, our team have been re-focusing on relational structure mapping, investigating its potential mechanisms across various analogy tasks, both abstract (semantically-lean) and more concrete (semantically-rich), using diverse methods (behavioral, correlational, eye-tracking, EEG). I will present the overview of our main findings. They suggest that structure mapping (1) consists of an incremental construction of the ultimate mental representation, (2) which strongly depends on working memory resources and reasoning ability, (3) even if as little as a single trivial relation needs to be represented mentally. The effective mapping (4) is related to the slowest brain rhythm – the delta band (around 2-3 Hz) – suggesting its highly integrative nature. Finally, we have developed a new task – Graph Mapping – which involves pure mapping of two explicit relational structures. This task allows for precise investigation and manipulation of the mapping process in experiments, as well as is one of the best proxies of individual differences in reasoning ability. Structure mapping is as crucial to analogy as Gentner advocated, and perhaps it is crucial to cognition in general.

The development of circuit-based therapeutics to treat neurological and neuropsychiatric diseases require detailed localization and understanding of electrophysiological signals in the human brain. Electrodes can record and stimulate circuits in many ways, and we often rely on non-invasive imaging methods to predict the location to implant electrodes. However, electrophysiological and imaging signals measure the underlying tissue in a fundamentally different manner. To integrate multimodal data and benefit from these complementary measurements, I will describe an approach that considers how different measurements integrate signals across the underlying tissue. I will show how this approach helps relate fMRI and intracranial EEG measurements and provides new insights into how electrical stimulation influences human brain networks.

The brain combines signals across the eyes. This process is well-characterized for the perceptual anatomical pathway through V1 that primarily codes contrast, where interocular normalization ensures that responses are approximately equal for monocular and binocular stimulation. But we have much less understanding of how luminance is combined binocularly, both in the cortex and in subcortical structures that govern pupil diameter. Here I will describe the results of experiments using a novel combined EEG and pupillometry paradigm to simultaneously index binocular combination of luminance flicker in parallel pathways. The results show evidence of a more linear process than for spatial contrast, that may reflect different operational constraints in distinct anatomical pathways.

It has long been established that the hippocampus plays a crucial role for episodic memory. As opposed to the modular approach, now it is generally assumed that being a complex structure, the HC performs multiplex interconnected functions, whose hierarchical organization provides basis for the higher cognitive functions such as semantics-based encoding and retrieval. However, the «where, when and how» properties of distinct memory aspects within and outside the HC are still under debate. Here we used a visual associative memory task as a probe to test the hypothesis about the differential involvement of the rostral and caudal portions of the human hippocampus in memory encoding, recognition and associative recall. In epilepsy patients implanted with stereo-EEG, we show that at retrieval the rostral HC is selectively active for recognition memory, whereas the caudal HC is selectively active for the associative memory. Low frequency desynchronization and high frequency synchronization characterize the temporal dynamic in encoding and retrieval. Therefore, we describe here anatomical segregation in the hippocampal contributions to associative and recognition memory.

The view of human brain function has drastically shifted over the last decade, owing to the observation that the majority of brain activity is intrinsic rather than driven by external stimuli or cognitive demands. Specifically, all brain regions continuously communicate in spatiotemporally organized patterns that constitute the functional connectome, with consequences for cognition and behavior. In this talk, I will argue that another shift is underway, driven by new insights from synergistic interrogation of the functional connectome using different acquisition methods. The human functional connectome is typically investigated with functional magnetic resonance imaging (fMRI) that relies on the indirect hemodynamic signal, thereby emphasizing very slow connectivity across brain regions. Conversely, more recent methodological advances demonstrate that fast connectivity within the whole-brain connectome can be studied with real-time methods such as electroencephalography (EEG). Our findings show that combining fMRI with scalp or intracranial EEG in humans, especially when recorded concurrently, paints a rich picture of neural communication across the connectome. Specifically, the connectome comprises both fast, oscillation-based connectivity observable with EEG, as well as extremely slow processes best captured by fMRI. While the fast and slow processes share an important degree of spatial organization, these processes unfold in a temporally independent manner. Our observations suggest that fMRI and EEG may be envisaged as capturing distinct aspects of functional connectivity, rather than intermodal measurements of the same phenomenon. Infraslow fluctuation-based and rapid oscillation-based connectivity of various frequency bands constitute multiple dynamic trajectories through a shared state space of discrete connectome configurations. The multitude of flexible trajectories may concurrently enable functional connectivity across multiple independent sets of distributed brain regions.

Playing action video games involves both explicit (conscious) and implicit (non-conscious) expectations of timed events, such as the appearance of foes. While studies revealed that explicit attention skills are improved in action video game players (VGPs), their implicit skills remained untested. To this end, we investigated explicit and implicit temporal processing in VGPs and non-VGPs (control participants). In our variable foreperiod task, participants were immersed in a virtual reality and instructed to respond to a visual target appearing at variable delays after a cue. I will present behavioral, oculomotor and EEG data and discuss possible markers of the implicit passage of time and explicit temporal attention processing. All evidence indicates that VGPs have enhanced implicit skills to track the passage of time, which does not require conscious attention. Thus, action video game play may improve a temporal processing found altered in psychopathologies, such as schizophrenia. Could digital (game-based) interventions help remediate temporal processing deficits in psychiatric populations?

The application of neuroimaging methods to marketing has recently gained lots of attention. In analyzing consumer behaviors, the inclusion of neuroimaging tools and methods is improving our understanding of consumer’s preferences. Human emotions play a significant role in decision making and critical thinking. Emotion classification using EEG data and machine learning techniques has been on the rise in the recent past. We evaluate different feature extraction techniques, feature selection techniques and propose the optimal set of features and electrodes for emotion recognition.Affective neuroscience research can help in detecting emotions when a consumer responds to an advertisement. Successful emotional elicitation is a verification of the effectiveness of an advertisement. EEG provides a cost effective alternative to measure advertisement effectiveness while eliminating several drawbacks of the existing market research tools which depend on self-reporting. We used Graph theoretical principles to differentiate brain connectivity graphs when a consumer likes a logo versus a consumer disliking a logo. The fusion of EEG and sentiment analysis can be a real game changer and this combination has the power and potential to provide innovative tools for market research.

Estimating intervals is essential for adaptive behavior and decision-making. Although several theoretical models have been proposed to explain how the brain keeps track of time, there is still no evidence toward a single one. It is often hard to compare different models due to their overlap in behavioral predictions. For this reason, several studies have looked for neural signatures of temporal processing using methods such as electrophysiological recordings (EEG). However, for this strategy to work, it is essential to have consistent EEG markers of temporal processing. In this talk, I'll present results from several studies investigating how temporal information is encoded in the EEG signal. Specifically, across different experiments, we have investigated whether different neural signatures of temporal processing (such as the CNV, the LPC, and early ERPs): 1. Depend on the task to be executed (whether or not it is a temporal task or different types of temporal tasks); 2. Are encoding the physical duration of an interval or how much longer/shorter an interval is relative to a reference. Lastly, I will discuss how these results are consistent with recent proposals that approximate temporal processing with decisional models.

Cognitive models of timing often include a pacemaker analogue whose ticks are accumulated to form an internal representation of time, and a threshold that determines when a target duration has elapsed. However, clear EEG manifestations of these abstract components have not yet been identified. We measured the EEG of subjects while they performed a temporal bisection task in which they were requested to categorize visual stimuli as short or long in duration. We report an ERP component whose amplitude depends monotonically on the stimulus duration. The relation of the ERP amplitude and stimulus duration can be captured by a simple model, adapted from a known drift-diffusion model for time perception. It includes a noisy accumulator that starts with the stimulus onset and a threshold. If the threshold is reached during stimulus presentation, the stimulus is categorized as "long", otherwise the stimulus is categorized as "short". At the stimulus offset, a response proportional to the distance to the threshold is emitted. This simple model has two parameters that fit both the behavior and ERP amplitudes recorded in the task. Two subsequent experiments replicate and extend this finding to another modality (touch) as well as to different time ranges (subsecond and suprasecond), establishing the described ERP component as a useful handle on the cognitive processes involved in temporal decisions.

Cognitive control allows us to think and behave flexibly based on our context and goals. Most theories of cognitive control propose a control representation that enables the same input to produce different outputs contingent on contextual factors. In this talk, I will focus on an important property of the control representation's neural code: its representational dimensionality. Dimensionality of a neural representation balances a basic separability/generalizability trade-off in neural computation. This tradeoff has important implications for cognitive control. In this talk, I will present initial evidence from fMRI and EEG showing that task representations in the human brain leverage both ends of this tradeoff during flexible behavior.

To survive in a rapidly dynamic world, the brain predicts the future state of the world and proactively adjusts perception, attention and action. A key to efficient interaction is to predict and prepare to not only “where” and “what” things will happen, but also to “when”. I will present studies in healthy and neurological populations that investigated the cognitive architecture and neural basis of temporal anticipation. First, influential ‘entrainment’ models suggest that anticipation in rhythmic contexts, e.g. music or biological motion, uniquely relies on alignment of attentional oscillations to external rhythms. Using computational modeling and EEG, I will show that cortical neural patterns previously associated with entrainment in fact overlap with interval timing mechanisms that are used in aperiodic contexts. Second, temporal prediction and attention have commonly been associated with cortical circuits. Studying neurological populations with subcortical degeneration, I will present data that point to a double dissociation between rhythm- and interval-based prediction in the cerebellum and basal ganglia, respectively, and will demonstrate a role for the cerebellum in attentional control of perceptual sensitivity in time. Finally, using EEG in neurodegenerative patients, I will demonstrate that the cerebellum controls temporal adjustment of cortico-striatal neural dynamics, and use computational modeling to identify cerebellar-controlled neural parameters. Altogether, these findings reveal functionally and neural context-specificity and subcortical contributions to temporal anticipation, revising our understanding of dynamic cognition.

In a famous philosophical paradox, Buridan's ass perishes because he is equally hungry and thirsty, and cannot make up his mind whether to first drink or eat. We are faced daily with the need to pick between alternatives that are equally attractive (or not) to us. What are the processes that allow us to avoid paralysis and to rapidly select between such equal options when there are no preferences or rational reasons to rely on? One solution that was offered is that although on a higher cognitive level there is symmetry between the alternatives, on a neuronal level the symmetry does not maintain. What is the nature of this asymmetry of the neuronal level? In this talk I will present experiments addressing this important phenomenon using measures of human behavior, EEG, EMG and large scale neural network modeling, and discuss mechanisms involved in the process of intention formation and execution, in the face of alternatives to choose from. Specifically, I will show results revealing the temporal dynamics of rapid intention formation and, moreover, ‘change of intention’ in a free choice picking scenario, in which the alternatives are on a par for the participant. The results suggest that even in arbitrary choices, endogenous or exogenous biases that are present in the neural system for selecting one or another option may be implicitly overruled; thus creating an implicit and non-conscious ‘change of mind’. Finally, the question is raised: in what way do such rapid implicit ‘changes of mind’ help retain one’s self-control and free-will behavior?

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.

Multisensory perception is often studied through the effects of inter-sensory conflict, such as in the McGurk effect, the Ventriloquist illusion, and the Rubber Hand Illusion. Moreover, Bayesian approaches to cue fusion and causal inference overwhelmingly draw on cross-modal conflict to measure and to model multisensory perception. Given the prevalence of conflict, it is remarkable that accounts of multisensory perception have so far neglected the theory of conflict monitoring and cognitive control, established about twenty years ago. I hope to make a case for the role of conflict monitoring and resolution during multisensory perception. To this end, I will present EEG and fMRI data showing that cross-modal conflict in speech, resulting in either integration or segregation, triggers neural mechanisms of conflict detection and resolution. I will also present data supporting a role of these mechanisms during perceptual conflict in general, using Binocular Rivalry, surrealistic imagery, and cinema. Based on this preliminary evidence, I will argue that it is worth considering the potential role of conflict in multisensory perception and its incorporation in a causal inference framework. Finally, I will raise some potential problems associated with this proposal.

Daily caffeine consumption and chronic sleep restriction are highly prevalent in society. It is well established that acute caffeine intake under controlled conditions enhances vigilance and promotes wakefulness but can also delay sleep initiation and reduce electroencephalographic (EEG) markers of sleep intensity, particularly in susceptible individuals. To investigate whether these effects are also present during chronic consumption of coffee/caffeine, we recently conducted several complementary studies. We examined whether repeated coffee intake in dose and timing mimicking ‘real world’ habits maintains simple and complex attentional processes during chronic sleep restriction, such as during a busy work week. We found in genetically caffeine-sensitive individuals that regular coffee (300 mg caffeine/day) benefits most attentional tasks for 3-4 days when compared to decaffeinated coffee. Genetic variants were also used in the population-based HypnoLaus cohort, to investigate whether habitual caffeine consumption causally affects time to fall asleep, number of awakenings during sleep, and EEG-derived sleep intensity. The multi-level statistical analyses consistently showed that sleep quality was virtually unaffected when >3 caffeine-containing beverages/day were compared to 0-3 beverages/day. This conclusion was further corroborated by quantifying the sleep EEG in the laboratory in habitual caffeine consumers. Compared to placebo, daily intake of 3 x 150 mg caffeine over 10 days did not strongly impair nocturnal sleep nor subjective sleep quality in good sleepers. Finally, we tested whether an engineered delayed, pulsatile-release caffeine formula can improve the quality of morning awakening in sleep-restricted volunteers. We found that 160 mg caffeine taken at bedtime ameliorated the quality of awakening, increased positive and reduced negative affect scores, and promoted sustained attention immediately upon scheduled wake-up. Such an approach could prevent over-night caffeine withdrawal and provide a proactive strategy to attenuate disabling sleep inertia. Taken together, the studies suggest that common coffee/caffeine intake habits can transiently attenuate detrimental consequences of reduced sleep virtually without disturbing subjective and objective markers of sleep quality. Nevertheless, coffee/caffeine consumption cannot compensate for chronic sleep restriction.

A recent formulation of predictive coding theory proposes that a subset of neurons in each cortical area encodes sensory prediction errors, the difference between predictions relayed from higher cortex and the sensory input. Here, we test for evidence of prediction error responses in spiking responses and local field potentials (LFP) recorded in primary visual cortex and area V4 of macaque monkeys, and in complementary electroencephalographic (EEG) scalp recordings in human participants. We presented a fixed sequence of visual stimuli on most trials, and violated the expected ordering on a small subset of trials. Under predictive coding theory, pattern-violating stimuli should trigger robust prediction errors, but we found that spiking, LFP and EEG responses to expected and pattern-violating stimuli were nearly identical. Our results challenge the assertion that a fundamental computational motif in sensory cortex is to signal prediction errors, at least those based on predictions derived from temporal patterns of visual stimulation.

In nature, sensory inputs are often highly structured, and statistical regularities of these signals can be extracted to form expectation about future sensorimotor associations, thereby optimizing behavior. One of the fundamental questions in neuroscience concerns the neural computations that underlie these probabilistic sensorimotor processing. Through a recurrent neural network (RNN) model and human psychophysics and electroencephalography (EEG), the present study investigates circuit mechanisms for processing probabilistic structures of sensory signals to guide behavior. We first constructed and trained a biophysically constrained RNN model to perform a series of probabilistic decision-making tasks similar to paradigms designed for humans. Specifically, the training environment was probabilistic such that one stimulus was more probable than the others. We show that both humans and the RNN model successfully extract information about stimulus probability and integrate this knowledge into their decisions and task strategy in a new environment. Specifically, performance of both humans and the RNN model varied with the degree to which the stimulus probability of the new environment matched the formed expectation. In both cases, this expectation effect was more prominent when the strength of sensory evidence was low, suggesting that like humans, our RNNs placed more emphasis on prior expectation (top-down signals) when the available sensory information (bottom-up signals) was limited, thereby optimizing task performance. Finally, by dissecting the trained RNN model, we demonstrate how competitive inhibition and recurrent excitation form the basis for neural circuitry optimized to perform probabilistic information processing.

Electro- and magneto-encephalography (EEG/MEG) are the leading methods to non-invasively record human neural dynamics with millisecond temporal resolution. However, it can be extremely difficult to infer the underlying cellular and circuit level origins of these macro-scale signals without simultaneous invasive recordings. This limits the translation of E/MEG into novel principles of information processing, or into new treatment modalities for neural pathologies. To address this need, we developed the Human Neocortical Neurosolver (HNN: https://hnn.brown/edu ), a new user-friendly neural modeling tool designed to help researchers and clinicians interpret human imaging data. A unique feature of HNN’s model is that it accounts for the biophysics generating the primary electric currents underlying such data, so simulation results are directly comparable to source localized data. HNN is being constructed with workflows of use to study some of the most commonly measured E/MEG signals including event related potentials, and low frequency brain rhythms. In this talk, I will give an overview of this new tool and describe an application to study the origin and meaning of 15-29Hz beta frequency oscillations, known to be important for sensory and motor function. Our data showed that in primary somatosensory cortex these oscillations emerge as transient high power ‘events’. Functionally relevant differences in averaged power reflected a difference in the number of high-power beta events per trial (“rate”), as opposed to changes in event amplitude or duration. These findings were consistent across detection and attention tasks in human MEG, and in local field potentials from mice performing a detection task. HNN modeling led to a new theory on the circuit origin of such beta events and suggested beta causally impacts perception through layer specific recruitment of cortical inhibition, with support from invasive recordings in animal models and high-resolution MEG in humans. In total, HNN provides an unpresented biophysically principled tool to link mechanism to meaning of human E/MEG signals.

At any given moment the brain receives more sensory information than it can use to guide adaptive behaviour, creating the need for mechanisms that promote efficient processing of incoming sensory signals. One way in which the brain might reduce its sensory processing load is to encode successive presentations of the same stimulus in a more efficient form, a process known as neural adaptation. Conversely, when a stimulus violates an expected pattern, it should evoke an enhanced neural response. Such a scheme for sensory encoding has been formalised in predictive coding theories, which propose that recent experience establishes expectations in the brain that generate prediction errors when violated. In this webinar, Professor Jason Mattingley will discuss whether the encoding of elementary visual features is modulated when otherwise identical stimuli are expected or unexpected based upon the history of stimulus presentation. In humans, EEG was employed to measure neural activity evoked by gratings of different orientations, and multivariate forward modelling was used to determine how orientation selectivity is affected for expected versus unexpected stimuli. In mice, two-photon calcium imaging was used to quantify orientation tuning of individual neurons in the primary visual cortex to expected and unexpected gratings. Results revealed enhanced orientation tuning to unexpected visual stimuli, both at the level of whole-brain responses and for individual visual cortex neurons. Professor Mattingley will discuss the implications of these findings for predictive coding theories of sensory encoding. Professor Jason Mattingley is a Laureate Fellow and Foundation Chair in Cognitive Neuroscience at The University of Queensland. His research is directed toward understanding the brain processes that support perception, selective attention and decision-making, in health and disease.