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Human Intracranial Cognitive Neurophysiology

The goal of the Helfrich lab is to unravel the neural network mechanisms supporting higher cognitive functions and their disturbances underlying neuropsychiatric disorders. We study the functional architecture of human cognition with a spatiotemporal resolution spanning single units to large-scale network activity. In particular, we seek to understand context-dependent, goal-directed behavior in humans through the study of neural network dynamics with a particular emphasis on prefrontal cortex (PFC) physiology. The key hypothesis is that context dependent endogenous brain activity shapes cognitive processing in different cortical states, i.e. wakefulness or sleep. A core interest is the systematic investigation of the functional network architecture of cortico-cortical and subcortico-cortical interactions supporting cognitive processes such as attention and memory and their impairment in healthy aging and neurodegenerative diseases.

Currently, much of our understanding of the neural basis of cognition stems from invasive primate recordings or non-invasive recordings in humans. The limited spatiotemporal resolution of non-invasive imaging hampers scientific progress in our understanding of health and disease. Human intracranial electrophysiology has the promise of significant insights into the neural mechanisms that guide behavior. Several clinical procedures provide the unique opportunity to record directly from the human brain at the single neuron or population level. A key goal of our lab is to bridge the gap between different imaging modalities in different species. Translationally, we integrate cognitive and clinical neurophysiology to increase our understanding of cognitive decline and reduced arousal levels such as sleep, anesthesia and coma.

If you are interested in a Bachelor, Master or PhD thesis in the lab, please send an email stating your research interests and your CV to or check the section "Open positions" below.

Research projects
Open positions


I. Rhythmic building blocks of human attention: How network oscillations link perception and action.

Attention is a fundamental cognitive function necessary to efficiently translate 
sensory experiences into goal-directed
. Traditionally, attention has been conceptualized as a constant spotlight that amplifies behaviorally-relevant information. Recently, several lines of inquiry probing attention on a fine-grained temporal scale revealed frequency-specific behavioral fluctuations that align with ongoing brain oscillations, indicating that attention is a discrete process. Our aim is to understand the structural and functional basis as well as the physiologic purpose of attentional rhythmic fluctuations.

See alsoHelfrich et al. (2018b) Neuron, Helfrich et al. (2019) Current Opinion in Psychology


II. Context-dependent predictive processing in human prefrontal cortex.

Over the last few decades, several lines of research indicated that the prefrontal cortex (PFC) provides the structural basis for goal-directed behavior based on endogenous predictions, but its functional architecture is not well understood. Our goal is to investigate how predictions are implemented in the human brain to optimize sensory processing and goal-directed behavior.

Background reading Helfrich and Knight (2016) Trends in Cognitive Science; Helfrich et al. (2017) PNAS


III. (Patho-) Physiology of human memory networks during wakefulness and sleep

Hippocampus-Prefrontal interactions are central to memory formation in the human brain. Critically, this network also constitutes a predilection site for various pathological entities that are associated with memory deficits. Our goal is to further dissect and understand the network circuitry underlying memory disorders in various patient populations (epilepsy, stroke and degenerative diseases)

Additional information: Helfrich et al. (2018a) Neuron; Winer, Mander, Helfrich et al. (2019) JNeurosci


IV. Principles of neuronal network organization in the sleeping and the unconscious (anesthesia, coma) brain.

How do different network states impact different behavioral states? Understanding principles of network organization is critical to understand disorders of consciousness. We will work with several patient populations to understand large-scale network mechanisms underlying reduced arousal states.

See also Helfrich et al. (2019) Nature Communications; Lendner, Helfrich et al. (2020) preprinted on the biorxiv

Research Group
Dr. Michael Hahn
Dr. Michael HahnPostdoc
Human Intracranial Cognitive Neurophysiology
Dr. Dr. Randolph Helfrich
Dr. Dr. Randolph HelfrichPhysician, Junior Research Group Leader
Human Intracranial Cognitive Neurophysiology
07071 29-61898 
 Markus Kopf
Markus KopfMD Student
Human Intracranial Cognitive Neurophysiology
Dr. Janna Lendner
Dr. Janna LendnerPhysician
Human Intracranial Cognitive Neurophysiology
 Isabel Raposo
Isabel RaposoPhD Student
Human Intracranial Cognitive Neurophysiology
 Jan Weber
Jan WeberPhD Student
Human Intracranial Cognitive Neurophysiology
Dr. Frank van Schalkwijk
Dr. Frank van SchalkwijkPostDoc
Human Intracranial Cognitive Neurophysiology


Key Publications



Helfrich, R.F., Lendner J.D., Mander B.A., Guillen H., Paff M., Mnatsakanyan L., Vadera S., Walker M.P., Lin J.J., Knight R.T. (2019). Bidirectional Prefrontal-Hippocampal Dynamics Organize Information Transfer during Sleep in Humans. Nature Communications


Helfrich, R.F., Fiebelkorn, I.C., Szczepanski, S.M., Lin, J.J., Parvizi, J., Knight, R.T., and Kastner, S. (2018b). Neural Mechanisms of Sustained Attention Are Rhythmic. Neuron

Helfrich, R.F., Mander, B.A., Jagust, W.J., Knight, R.T., and Walker, M.P. (2018a). Old Brains Come Uncoupled in Sleep: Slow Wave-Spindle Synchrony, Brain Atrophy, and Forgetting. Neuron


Helfrich, R.F., Huang, M., Wilson, G., and Knight, R.T. (2017). Prefrontal cortex modulates posterior alpha oscillations during top-down guided visual perception. PNAS


Helfrich, R.F., and Knight, R.T. (2016). Oscillatory Dynamics of Prefrontal Cognitive Control. Trends in Cognitive Sciences

Link to:

Research group leader
Dr. Dr. Randolph HelfrichPhone +49 (0)7071 29-61898Randolph.Helfrich@med.uni-tuebingen.deAddress

Center of Neurology
Hertie Institute for Clinical Brain Research

Hoppe-Seyler-Str. 3
72076 Tübingen

Phone: +49 (0)7071 29-80442