Biology subjects

Klein-Flugge, M.

Publications and source records attributed to Klein-Flugge, M..

8 recordsLinked to original sources

bioRxiv2026

Frontotemporal cortex flexibly adapts latent structural representations

Humans excel at navigating complex environments by forming abstract structural representations that can be flexibly updated when environments change. Here, we examine how the brain dynamically reconfigures these internal models in response to covert changes in latent hierarchies. Using a novel inference task and fMRI repetition suppression, we find that stable relational knowledge is encoded in medial orbitofrontal cortex (mOFC), while structural changes trigger transient representations across hippocampal and prefrontal regions. Newly inferred associations are first encoded in anterior medial frontal cortex (amFC) and migrate ventrally to mOFC when settling. In contrast, outdated associations transiently engage frontopolar cortex and hippocampus, with the hippocampus, but not frontal areas, retaining a residual memory trace. Notably, the strength of early novel signals in amFC and hippocampus tracks individual differences in behavioural adaptation. Together, these results characterise mechanisms supporting adaptive structural reconfiguration in the human brain, with implications for cognitive inflexibility in psychiatric disorders. SIGNIFICANCE STATEMENTThe brain relies on internal models of hidden environmental structure, yet how these models are revised when the world changes remains unclear. We developed a novel task and neuroimaging approach that allowed us to trace the emergence, maintenance, and dissolution of latent structural representations in humans. Stable representations were encoded in medial orbitofrontal cortex, whereas newly formed and outdated associations followed distinct temporal trajectories across frontal and hippocampal regions. Outdated representations transiently recruited frontopolar cortex but persisted in hippocampus after becoming behaviorally irrelevant. Neural signatures of updating predicted individual differences in adaptation, revealing candidate mechanisms through which cognitive flexibility, and its impairment in psychiatric disorders, may arise.

neuroscience↗

bioRxiv2025

Distinct roles of hippocampus and neocortex in symbolic compositional generalization

Humans can combine symbols to generate new meanings. Here, we studied the regional neural mechanisms that might make this possible. We asked participants to combine two discrete, symbolic features (a shape and a colour) to make a novel spatial inference. BOLD data suggested that the hippocampus encoded elementary visual attributes in a high-dimensional, parallel format that permitted flexible individuation. In ventromedial prefrontal cortex (vmPFC), posterior parietal cortex (PPC) and primary visual cortex (V1), neural patterns for novel stimuli (composites) could be predicted as a linear combination of signals for familiar stimuli (elements). In vmPFC, this composition occurred in a high-dimensional format, but in PPC and V1, it took place in a low-dimensional, spatial, response-consistent frame of reference. These data offer new insights into the neural circuit underlying compositional generalization.

neuroscience↗

bioRxiv2022

Action initiation and punishment learning differ from childhood to adolescence while reward learning remains stable

Theoretical and empirical accounts suggest that adolescence is associated with heightened reward learning and impulsivity. Experimental tasks and computational models that can dissociate reward learning from the tendency to initiate actions impulsively (action initiation bias) are thus critical to characterise the mechanisms that drive developmental differences. However, existing work has rarely quantified both learning ability and action initiation, or it has tested small samples. Here, using computational modelling of a learning task collected from a large sample (N=742, 9-18 years, 11 countries), we tested differences in reward and punishment learning and action initiation from childhood to adolescence. Computational modelling revealed that whilst punishment learning rates increased with age, reward learning remained stable. In parallel, action initiation biases decreased with age. Results were similar when considering pubertal stage instead of chronological age. We conclude that heightened reward responsivity in adolescence can reflect differences in action initiation rather than enhanced reward learning.

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bioRxiv2020

Entraining corticocortical plasticity changes oscillatory activity in action control and inhibition

Oscillatory activity may reflect interactions between brain areas[1]. Here we tested whether inducing corticocortical plasticity in a specific set of connections changes oscillatory activity and cortico-cortical interactions and, if this is the case, whether the changes manifest in a manner that is behaviour state-dependent. We either increased or decreased the influence of activity in human ventral premotor cortex (PMv) over activity in primary motor cortex (M1) using cortico-cortical paired associative stimulation (ccPAS)[2, 3]. Before and after stimulation participants performed a Go/No-Go task. While M1 TMS pulses revealed the excitatory state of the motor system at specific time points, the electroencephalogram (EEG) revealed the evolution of oscillatory activity dynamics in the motor system over several hundreds of milliseconds before, during, and after each movement. Augmenting cortical connectivity between PMv and M1, by evoking synchronous pre- and postsynaptic activity in the PMv-M1 pathways, led to a state-dependent modulation of the causal influence of PMv over M1, and at the same time, enhanced oscillatory beta and theta rhythms in Go and No-Go trials, respectively. No changes were observed in the alpha rhythm. The plasticity induction effect was dependent on PMv-M1 stimulation order; the opposite patterns of results were observed after an equal amount of stimulation of PMv and M1 but applied in a temporal pattern that did not augment PMvs influence over M1. These results are consistent with Hebbian principles of synaptic plasticity[4] and show that artificial manipulation of cortico-cortical connectivity produces state-dependent functional changes in the spectral fingerprints of the motor circuit.

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bioRxiv2020

Projections of non-invasive human recordings into state space show unfolding of spontaneous and over-trained choice

Choices rely on a transformation of sensory inputs into motor responses. Using invasive single neuron recordings, the evolution of a choice process has been tracked by projecting population neural responses into state spaces. Here we develop an approach that allows us to recover state space trajectories on a millisecond timescale in non-invasive human recordings. We selectively suppress activity related to relevant and irrelevant sensory inputs and response direction in magnetoencephalography data acquired during context-dependent choices. Recordings from premotor cortex show a smooth progression from sensory input encoding to response encoding. In contrast to previous macaque recordings, information related to choice-irrelevant features is represented more weakly than choice-relevant sensory information. To test whether this mechanistic difference between species is caused by extensive overtraining common in non-human primate studies, we trained humans on >20,000 trials of the task. Choice-irrelevant features were still weaker than relevant features in premotor cortex after overtraining.

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bioRxiv2019

Neural signatures of model-free learning when avoiding harm to self and other

Moral behaviour requires learning how our actions help or harm others. Theoretical accounts of learning propose a key division between model-free algorithms that efficiently cache outcome values in actions and model-based algorithms that prospectively map actions to outcomes, a distinction that may be critical for moral learning. Here, we tested the engagement of these learning mechanisms and their neural basis as participants learned to avoid painful electric shocks for themselves and a stranger. We found that model-free learning was prioritized when avoiding harm to others compared to oneself. Model-free prediction errors for others relative to self were tracked in the thalamus/caudate at the time of the outcome. At the time of choice, a signature of model-free moral learning was associated with responses in subgenual anterior cingulate cortex (sgACC), and resisting this model-free influence was predicted by stronger connectivity between sgACC and dorsolateral prefrontal cortex. Finally, multiple behavioural and neural correlates of model-free moral learning varied with individual differences in moral judgment. Our findings suggest moral learning favours efficiency over flexibility and is underpinned by specific neural mechanisms.

neuroscience↗

bioRxiv2018

The macaque anterior cingulate cortex translates counterfactual choice value into actual behavioral change

The neural mechanisms mediating sensory-guided decision making have received considerable attention but animals often pursue behaviors for which there is currently no sensory evidence. Such behaviors are guided by internal representations of choice values that have to be maintained even when these choices are unavailable. We investigated how four macaque monkeys maintained representations of the value of counterfactual choices - choices that could not be taken at the current moment but which could be taken in the future. Using functional magnetic resonance imaging, we found two different patterns of activity co-varying with values of counterfactual choices in a circuit spanning hippocampus, anterior lateral prefrontal cortex, and anterior cingulate cortex (ACC). ACC activity also reflected whether the internal value representations would be translated into actual behavioral change. To establish the causal importance of ACC for this translation process, we used a novel technique, Transcranial Focused Ultrasound Stimulation, to reversibly disrupt ACC activity.

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bioRxiv2018

Offline impact of transcranial focused ultrasound on cortical activation in primates

To understand brain circuits it is necessary both to record and manipulate their activity. Despite increased availability of techniques for manipulating neural activity in rodents, manipulating neural activity in primates remains difficult. Here we show that a minimally invasive technique, transcranial focused ultrasound stimulation (TUS), induced offline changes to activity of circumscribed brain regions in the macaque. Applying TUS to the supplementary motor area or frontal polar cortex resulted in spatially specific patterns of activity change measurable with functional magnetic resonance imaging. In each case changes reflected each areas known network of interactions with the rest of the brain. Independent of these specific neural effects, TUS over these regions also induced widespread signal changes that might have a non-neuronal origin possibly mediated by the cerebral spinal fluid compartment. Although sustained for more than one hour beyond the 40s stimulation period, TUS effects were reversible and not associated with histological changes.\n\nHighlights O_LIMany studies of ultrasound neuromodulation focus on online effects in rodents.\nC_LIO_LIWe use fMRI connectivity to investigate its offline impact in the primate brain.\nC_LIO_LI40 s of ultrasound leads to a sustained, specific, reversible neural modulation.\nC_LIO_LIUltrasound caused a sharpening of the stimulated regions connectivity profile.\nC_LI\n\nIn BriefA new application of focused ultrasound safely modulates brain activation in primates for up to 2 hours after 40 seconds of stimulation. Ultrasound caused the stimulated area to interact more selectively with the rest of the brain.

neuroscience↗