Neuroplasticity, Synchrony and Cognition

Prof. Dr. Alexander Sack is the founder of the Brain Stimulation and Cognition group at Maastricht University. His research interests facilitate several topics.

Human cognition
This research focuses on the neurobiological and psychological principles underlying attention, memory and cognitive control - combining various brain research techniques, ranging from psychophysics and eye-tracking to functional Magnetic Resonance Imaging (fMRI), Electroencephalography (EEG), and Noninvasive Brain Stimulation (NIBS), especially Transcranial Magnetic (TMS) and Transcranial Electric Brain Stimulation (TES, including TDCS and TACS). 

We investigate the neural network dynamics underlying human cognition, aim to experimentally establish functional brain-cognition relationships, unmask and guide the highly dynamic network properties and enormous capacity, adaptivity, and flexibility of the human brain to compensate for any malfunction and to reorganise neural networks to maintain or regain functionality of cognition, as well as to use personalised, oscillatory- and network-based neuromodulation technologies to enhance cognitive performances in the healthy and diseased human brain.

Multimodal Cognitive Brain Stimulation
This research focuses on simultaneously combining noninvasive brain stimulation and neuroimaging techniques, including concurrent TMS – fMRI, concurrent TMS – EEG, concurrent TES – fMRI, concurrent TES – EEG, and concurrent TMS – EEG – fMRI. Sack’s group in Maastricht pioneered the development of simultaneously implemented TMS-fMRI-EEG during cognitive behavior, allowing to apply brain-stimulation while recording the individual brain network (fMRI) and oscillation (EEG) states of cognitively engaged participants. These multimodal brain stimulation approaches enable the direct and non-invasive in-vivo probing of brain-state dependent signal propagation within specific brain-wide cortico-subcortical networks and to study how temporal (oscillations) and spatial (brain-wide networks) coding dynamics interrelate. The noninvasive investigation of such oscillation-network coupling principles allows for subject-specific network research into dynamic cognitive circuits and their dysfunction.

State-dependence of noninvasive brain stimulation
This research focuses on the combination of brain stimulation and neuroimaging to systematically assess the brain state dependence of transcranial magnetic and transcranial electric brain stimulation technologies. The neurophysiological and cognitive effects of various rTMS and TES protocols are empirically assessed using fMRI and EEG in the context of either different experimentally induced brain states (e.g. cognitive states), and/or EEG-indexed spontaneous fluctuations of endogenous oscillatory resting brain states (e.g. phase-dependent network effects of TMS), and/or the neural state history (e.g. priming or preconditioning). The state-dependence of brain stimulation is also relevant for optimising protocols aimed at inducing neuroplasticity in the brain.

Brain Plasticity
This research focuses on developing and testing new brain stimulation protocols capable of inducing longer lasting neuroplastic changes. Although repetitive TMS is capable of inducing such longer lasting changes in cortical excitability, the frequency-dependence, state-dependence, and inter-subject variability remain poorly understood. We aim to contribute to a better understating of the mechanisms of neuroplasticity as induced by neuromodulation and brain stimulation technologies, hoping to reduce the currently still unsolved problem of intra-subject reliability and inter-subjkect variability.  This will not only inform us about the fundamental mechanism of brain plasticity in the context of human cognition, but also guide the development of innovative and optimised clinical protocols for treating various psychiatric and neurological disorders.   

Clinical Applications of Noninvasive Brain Stimulation
All research described above has direct and indirect implications also for the clinical applications of TMS and TES. Our group constantly aims to promote scientific research and collaboration in the field of applied noninvasive brain stimulation and its translation to clinical practice. As part of a large international network of academic hospitals and clinical practitioners, we are actively involved in bringing the gap between scientific research and clinical practice in the field of brain stimulation. These research include clinical research for using TMS and TES for the drug-free treatment of Depression, OCD, Neuropathic Pain, Stroke rehabilitation, Parkinson’s Disease, and Alzheimer’s Disease. We are always open for other clinical cooperation partners interested in expanding, optimising, and evaluating the indications for noninvasive brain stimulation. Please see also our external PhD programme. 

Prof. Dr. Peter de Weerd is the founder of the Perception, Attention, Learning and Memory group at Maastricht University. His research interests facilitate several topics.

Non-invasive brain stimulation (NIBS) can modulate neural activity and network excitability during and beyond the stimulation period. These sustained neuroplastic changes make NIBS a good treatment option in a variety of psychiatric, neurological and rehabilitation settings. Neglect rehabilitation after stroke is one of our key clinical applications of NIBS. Patients’ spontaneous functional brain reorganisation is often maladaptive, and we use TMS and tDCS to interchangeably suppress or activate hyper- or hypo-active parts of the network, restoring a healthy hemispheric symmetry and improving the recovery of function. Another clinical application of NIBS is in the treatment of neuropsychiatric disorders such as depression and OCD, where we focus on quantifying sustained neuroplastic improvements and on optimising existing treatment protocols. In these settings, we often work closely with the patient population and collaborate with local clinicians at the MUMC+ and Mondriaan hospitals.

Our experiences are temporally structured sequences of moments. Yet, we do not have an explicit sensory system for the passage of time. How we perceive and process those moments influences our recollection of “time”, which suggests that we reconstruct our sense of time from our memories. In turn, this affects how we abstract causal relations, value future goals, learn from repeated exposures or communicate our experiences to others. This research line investigates how we process and memorize temporal structure from perceptual content (and vice versa). To this end, we combine dedicated (online and lab-based) behavioural paradigms with computational modelling, functional neuroimaging (fMRI, EEG) and noninvasive brain stimulation (TMS, TES). We also combine the inherent and naturalistic temporal structure of narrative stimuli, such as movies and songs, with the highly controlled but artificially designed experimental designs of lab-based experiments. Our goal is to achieve a comprehensive and multi-level understanding of how the human brain creates a sense of time from experiences and how this affects our individual and social behaviour and cognition.

The brain is composed of many individual neurons, who’s collective activity give rise to our perception, experience and action. In this research line we use carefully designed psychophysics, eye-tracking and EEG experiments, together with invasive electrophysiology from human patients, to understand the link between neuronal and cognitive processes. We investigate the dynamic nature of visual perception and of information transmission between neurons from the perspective of weakly coupled oscillator theory, in which synchronisation strength is determined by moment-to-moment changes frequency differences and connectivity strengths. This perspective gives a new way to understand and analyse neuronal communication. Our understanding of neuronal processes is greatly enhanced by directly studying the properties of individual neurons, however invasive electrophysiology is only in the context performed in human participants of medical treatment. One such context is deep brain stimulation (DBS), in which stimulating electrodes are implanted in specific brain structures to effectively treat for a variety of otherwise untreatable conditions. Parkinson’s disease is the most common condition for which DBS is applied, however its use is rapidly expanding to a variety of other conditions, including epilepsy and tinnitus. Optimal treatment depends on precise targeting of the implant, guided by pre-operative imaging and intraoperative electrophysiological recordings of neuronal spikes and local field potentials. Studying these recordings, using the perspectives gained from our fundamental research into healthy participants, gives a unique view on the functioning of the human brain, with novel findings for both fundamental and medical research.

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique that is widely used in research to gain insights into brain function and in clinical practice to treat brain-based disorders. Successful TMS application critically depends on the use of adequate stimulation parameters and experimental designs. In many cases, this requires a personalised approach where TMS intensity and localization are tailored to the individual brain region of interest. This research line aims to advance TMS methodology by optimising stimulation parameters, developing robust procedures suitable for specific settings (clinic vs. lab), and implementing multimodal approaches that combine brain stimulation and neuroimaging to explore and validate the effects of TMS on the brain. This also requires awareness and careful implementation of experimental control conditions to prevent confounding (e.g. sensory effects of TMS).

Inhibitory control over unwanted thoughts, emotions and movements is essential for effective interaction with our environment. This becomes particularly evident when there is too little inhibition, as in obsessive-compulsive disorder or Tourette’s syndrome, or too much, as in Parkinson’s disease. Recent evidence links successful inhibition to the power of neural oscillations in the beta band (15-30Hz) in a circuit involving parts of the frontal cortex and the subthalamic nucleus. While this is an important step forward, it is not yet sufficient to develop effective neuromodulatory treatments for inhibitory control disorders. For that, we need to understand how the beta oscillations mediate neuronal communication within the fronto-subthalamic circuit. In this project, we address this challenging question through novel applications of transcranial alternating current stimulation (tACS). This non-invasive brain stimulation technique aligns neuronal oscillations to an oscillating low intensity electrical current applied to the brain. This external control over oscillatory power and phase allows us to investigate: the functional relevance of beta oscillatory phase, the causal role of interactions between beta oscillations and other frequency bands (‘cross-frequency coupling’) and the importance of synchrony within the network. In parallel, we are developing an innovative, non-invasive, treatment strategy for patients with inhibitory control deficits, by recording and modulating abnormal circuit activity in a closed-loop.

Rhythm and temporal information can be used to optimally predict when something is going to happen. However, temporal information also provides information about the exact content of information, that is temporal information does not only provide cues for when, but also for what. For both operations (tracking and coding temporal information) the same temporal brain dynamics are important, namely brain oscillations. How can the brain track continuously incoming information and simultaneously use the temporal dimension to code information? To do this the brain needs to compute in time as well as with time. This research line investigates how our brain can track temporal structure and how temporal dynamics in the brain are relevant for various cognitive functions such as memory, speech, and attention. We use EEG, MEG, ECoG, brain stimulation, and computational modelling. More information about this research line can be found here: https://tedyum.github.io/

This research line investigates the neurobiological and computational principles underlying the interaction between perception, memory, and consciousness. It examines how fleeting sensory inputs are transformed into stable, meaningful, and subjectively experienced representations, and how prior experiences - often outside of awareness - systematically shape what we see, remember, and decide.

Challenging the traditional separation between perception and memory, we conceptualise perception as an inherently constructive and predictive process that integrates sensory evidence with stored representations across multiple timescales. Using high-temporal-resolution electrophysiology (EEG, MEG, iEEG), psychophysics, eye tracking, machine learning, and computational modeling - alongside planned extensions to (ultra-high-field) fMRI - we identify the dynamic network mechanisms through which perceptual memories are maintained, transformed, and integrated across cortical hierarchies.

In the long term, this research line aims to develop a mechanistically grounded and empirically testable theory of perception-memory interactions that explains how subjective experience emerges from distributed neural dynamics and why it differs across individuals, with implications for learning, decision-making, and real-world cognition.

This research line focuses transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to study the neural mechanisms underlying higher cognitive functions, including attention, visual perception, and awareness. By directly modulating brain oscillations, the work aims to establish their causal role in cognition. A key focus is on the development of innovative TMS approaches, such as state-dependent stimulation tailored to individual brain dynamics as well as network-based protocols aimed at influencing entire cognitive networks rather than isolated brain regions.