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Doeller, C. F.

Publications and source records attributed to Doeller, C. F..

At least 37 records · Page 2Linked to original sources

The effects of task similarity during representation learning in brains and neural networks

The complexity of our environment poses significant challenges for adaptive behavior. Recognizing shared structures across tasks can theoretically improve learning through generalization. However, how such shared representations emerge and influence performance remains poorly understood. Contrary to expectations, our findings revealed that individuals trained on tasks with similar low-dimensional structures performed worse than those trained on dissimilar tasks. Magnetoencephalography revealed correlated neural representations in the samestructure group and anticorrelated ones in the different-structure group. Crucially, practice reduced this performance gap and shifted the neural representations of the tasks in the samestructure group towards anticorrelation, like those in the different-structure group. A neural network model trained on similar tasks replicated these findings: tasks with similar structures require more iterations to orthogonalize their representations. These results highlight a complex interplay between task similarity, neural dynamics, and behavior, challenging traditional assumptions about learning and generalization.

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Entorhinal grid-like codes for visual space during memory formation

Eye movements, such as saccades, allow us to gather information about the environment and, in this way, can shape memory. In non-human primates, saccades are associated with the activity of grid cells in the entorhinal cortex. Grid cells are essential for spatial navigation, but whether saccade-based grid-like signals play a role in human memory formation is currently unclear. Here, human participants underwent functional magnetic resonance imaging (fMRI) and continuous eye gaze monitoring while studying scene images. Recognition memory was probed immediately thereafter. Results revealed saccade-based grid-like codes in the left entorhinal cortex while participants studied the scene images, a finding that was replicated with an independent data set reported here. The grid-related effects were time-locked to activation increases in the frontal eye fields. Most importantly, saccade-based grid-like codes were associated with recognition memory, such that grid-like codes were lower the better participants performed in subsequently recognizing the scene images. Collectively, our findings suggest an entorhinal map of visual space that is timed with neural activity in oculomotor regions, supporting memory formation.

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The scope and limits of fine-grained category information in the ventral visual pathway

Humans can easily abstract incoming visual information into discrete semantic categories. Previous research employing functional MRI (fMRI) in humans has identified cortical organizing principles that allow not only for coarse-scale distinctions such as animate versus inanimate objects but also more fine-grained distinctions at the level of individual objects. This suggests that fMRI carries rather fine-grained information about individual objects. However, most previous work investigating fine-grained category representations either additionally included coarse-scale category comparisons of objects, which confounds fine-grained and coarse-scale distinctions, or only used a single exemplar of each object, which confounds visual and semantic information. To address these challenges, here we used multisession human fMRI (female and male) paired with a broad yet homogenous stimulus class of 48 terrestrial mammals, with 2 exemplars per mammal. Multivariate decoding and representational similarity analysis (RSA) revealed high image-specific reliability in low- and high-level visual regions, indicating stable representational patterns at the image level. In contrast, analyses across exemplars of the same animal yielded only small effects in the lateral occipital complex (LOC), indicating rather subtle category effects in this region. Variance partitioning with a deep neural network and shape model showed that across exemplar effects in EVC were largely explained by low-level visual appearance, while representations in LOC appeared to also contain higher category-specific information. These results suggest that representations typically measured with fMRI are dominated by image-specific visual or coarse-grained category information but indicate that commonly employed fMRI protocols may reveal subtle yet reliable distinctions between individual objects. Significance StatementWhile it has been suggested that functional MRI (fMRI) responses in ventral visual cortex carry fine-grained information about individual objects, much previous research has confounded fine-grained with coarse-scale category information or only used individual visual exemplars, which potentially confounds semantic and visual object information. Here we address these challenges in a multisession fMRI study where participants viewed a highly homogenous stimulus set of 48 land mammals with 2 exemplars per animal. Our results reveal a strong dominance of image-specific effects and additionally indicate subtle yet reliable category-specific effects in lateral occipital complex, underscoring the capacity of commonly employed fMRI protocols to uncover fine-grained visual information.

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Hippocampal-entorhinal cognitive maps and cortical motor system represent action plans and their outcomes

Efficiently interacting with the environment requires weighing and selecting among multiple alternative actions based on their associated outcomes. However, the neural mechanisms underlying these processes are still debated. We showed that forming relations between arbitrary action-outcome associations involved building a cognitive map. Using a novel immersive virtual reality paradigm, participants learned 2D abstract motor action-outcome associations and later compared action combinations while their brain activity was monitored with fMRI. We observed a hexadirectional modulation of the activity in entorhinal cortex while participants compared different action plans. Furthermore, hippocampal activity scaled with the 2D similarity between outcomes of these action plans. Conversely, the supplementary motor area (SMA) represented individual actions, showing a stronger response to overlapping action plans. Crucially, the connectivity between hippocampus and SMA was modulated by the similarity between the action plans, suggesting their complementary roles in action evaluation. These findings provide evidence for the role of cognitive maps in action selection, challenging classical models of memory taxonomy and its neural bases.

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Integrating episodic and spatial context signals in the hippocampus

Episodic and spatial memory are the two key components of the mnemonic system in humans. Episodic memory enables us to remember events from the past whereas spatial memory enables us to form a map-like representation of the environment. Interestingly, these seemingly different functions rely on the same brain structure: the hippocampus. Yet, how the hippocampus supports both at the same time remains unclear. Here, we tested the hypotheses that the hippocampus supports these two systems either via a common coding mechanism or via a parallel processing mechanism. To this end, we combined functional magnetic resonance imaging (fMRI) with an episodic life-simulation task and a spatial virtual reality task to manipulate episodic and spatial context associations of objects. We then investigated fMRI adaptation effects between these objects as a result of shared contexts. We found that the fMRI signal in the anterior hippocampus scaled with the combined prediction of shared episodic and spatial contexts, in line with the idea of a common coding mechanism. We found no evidence for a parallel processing mechanism, as there were no differences between episodic and spatial effects. The common coding effect for episodic and spatial memory dovetails with the broader notion of domain-general hippocampal cognitive maps.

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Symmetry and Generalization in Local Learning of Predictive Representations

In spatial cognition, the Successor Representation (SR) from reinforcement learning provides a compelling candidate of how predictive representations are used to encode space. In particular, hippocampal place cells are hypothesized to encode the SR. Here, we investigate how varying the temporal symmetry in learning rules influences those representations. To this end, we use a simple local learning rule which can be made insensitive to the temporal order. We analytically find that a symmetric learning rule results in a successor representation under a symmetrized version of the experienced transition structure. We then apply this rule to a two-layer neural network model loosely resembling hippocampal subfields CA3 - with a symmetric learning rule and recurrent weights - and CA1 - with an asymmetric learning rule and no recurrent weights. Here, when exposed repeatedly to a linear track, neurons in our model in CA3 show less shift of the centre of mass than those in CA1, in line with existing empirical findings. Investigating the functional benefits of such symmetry, we employ a simple reinforcement learning agent which may learn symmetric or classical successor representations. Here, we find that using a symmetric learning rule yields representations which afford better generalization, when the agent is probed to navigate to a new target without relearning the SR. This effect is reversed when the state space is not symmetric anymore. Thus, our results hint at a potential benefit of the inductive bias afforded by symmetric learning rules in areas employed in spatial navigation, where there naturally is a symmetry in the state space. Author summaryThe hippocampus is a brain region which plays a crucial role in spatial navigation for both animals and humans. Contemporarily, its thought to store predictive representations of the environment, functioning like maps that indicate the likelihood of visiting certain locations in the future. In our study, we used an artificial neural network model to learn these predictive representations by adjusting synaptic connections between neurons according to local learning rules. Unlike previous research, our model includes learning rules that are invariant to the temporal order of events, meaning they are symmetric with respect to the reversal of input timings. This approach produces predictive representations particularly useful for understanding spatial relationships, as navigating from one point to another is often equivalent to the reverse. Our model offers additional insights: it replicates observed properties of hippocampal cells and helps an artificial agent solve navigation tasks. The agent trained with our model not only learns to navigate but also generalizes better to new targets compared to traditional models. Our findings suggest that symmetric learning rules enhance the brains ability to create useful predictive maps for problems which are inherently symmetric, as is navigation.

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The hippocampus supports interpolation into new states during category abstraction

The hippocampus forms concepts by integrating multi-feature relations into a unified representation. A common yet unconfirmed assumption is that such cognitive maps afford interpolations to never-experienced states. We approach this question as a category-learning problem in which prototypes are omitted from training but guide category-based decisions in a subsequent feature-inference task. Consistent with behavior, missing inferred stimulus features were represented at prototypical values in neocortex. This cortical completion effect correlated with hippocampal responses, which in turn reflected the distance between imagined prototypes and experienced exemplars. This was paralleled by a learning-dependent grid-like representation of the underlying conceptual space in entorhinal cortex. Our results suggest that abstracted prototypes correspond to interpolated central states in a cognitive map that guide cortical pattern completion during category-based decisions.

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Phylogeny of neocortical-hippocampal projections provides insight in the nature of human memory

The study of cross-species differences in the organization of the cerebral cortex received significant attention during the past century. However, the evolutionary principles governing changes in brain connectivity and their impact on cognition remain poorly understood. In the current study, we analysed differences in anatomical input from the cerebral cortex to the hippocampal region across six species spanning more than 100 million years of mammalian evolution - the tenrec, rat, cat, marmoset, macaque, and human. Our results demonstrate that unlike direct transmodal cortical input, direct unimodal cortical input to the hippocampal region was selectively eliminated with the increase in brain size. Additionally, input from primary sensory regions was eliminated prior to input from non-primary sensory regions. Our findings suggest that hippocampus-related processes in different species operate on fundamentally different types of information, potentially underpinning cross-species differences in hippocampus-dependent cognition. Furthermore, our findings outline the evolutionary trajectory of the anatomical circuitry associating the human hippocampal region with the neocortex.

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Encoding of task regularities links grid-like signals to human timing behavior

Grid cells have been proposed to encode task regularities that allow predicting future states. Entorhinal grid-like signals might therefore mirror behavioral biases associated with relying on task regularities, like regression-to-the-mean biases in time estimation. Here, we tested this proposal using functional magnetic resonance imaging and a rapid timing task in humans. Indeed, trial-wise entorhinal activity reflected task accuracy and the degree to which interval estimates regressed towards the mean of all tested intervals. Grid-like signals were observed exclusively for the interval closest to the mean, which was explained by differences in temporal grid stability across intervals. Finally, both behavioral and entorhinal results were explained by a Bayesian observer model that assumes the integration of current-trial sensory evidence with prior expectations. Together, we find that entorhinal activity and grid-like signals reflect behavioral performance in a timing task, supporting the proposed role of grid cells in encoding task structure for predictive processing.

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Grid-like entorhinal representation of an abstract value space during prospective decision making

Everyday decisions require us to predict how valuable different choice options will be in the future. Prior studies have identified a cognitive map in the hippocampal-entorhinal system that encodes relationships between states and enables prediction of future states, but does not inherently convey value during prospective decision making. Here, we investigated whether the entorhinal cortex integrates relational information about changing values by representing an abstract value space. To this end, we combined fMRI with a prospective decision making task that required participants to track and predict changing values of two choice options in a sequence. Such a sequence formed a trajectory through an underlying two-dimensional value space. Our results show that participants successfully integrated and extrapolated changes along the two value dimensions. Participants choice behavior was explained by a prospective reinforcement learning model and the degree to which they updated values over time correlated with self-reported navigational abilities and preferences. Crucially, while participants traversed the abstract value space, the entorhinal cortex exhibited a grid-like representation, with the phase of the hexadirectional fMRI signal (i.e., the orientation of the estimated grid) being aligned to the most informative axis through the value space. A network of brain regions, including the ventromedial prefrontal cortex (vmPFC), tracked the prospective value difference between options and the occipital-temporal cortex represented the more valuable option. These findings suggest that the entorhinal grid system might support the prediction of future values by representing a cognitive map, which might be used to generate lower-dimensional signals of the value difference between options and their identities for choices. Thus, these findings provide novel insight for our understanding of cognitive maps as a mechanism to guide prospective decision making in humans.

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A combined DTI-fMRI approach for optimizing the delineation of posteromedial vs. anterolateral entorhinal cortex

In the entorhinal cortex (EC), attempts have been made to identify the human homologue regions of the medial (MEC) and lateral (LEC) subdivision using either functional magnetic resonance imaging (fMRI) or diffusion tensor imaging (DTI). However, there are still discrepancies between entorhinal subdivisions depending on the choice of connectivity seed regions and the imaging modality used. While DTI can be used to follow the white matter tracts of the brain, fMRI can identify functionally connected brain regions. In this study, we used both DTI and resting-state fMRI in 103 healthy adults to investigate both structural and functional connectivity between the EC and associated cortical brain regions. Differential connectivity with these regions was then used to predict the locations of the human homologues of MEC and LEC. Our results from combining DTI and fMRI support a subdivision into posteromedial (pmEC) and anterolateral (alEC) EC and reveal a confined border between the pmEC and alEC. Furthermore, the EC subregions obtained by either imaging modality showed similar distinct connectivity patterns: While pmEC showed increased connectivity preferentially with the default mode network, the alEC exhibited increased connectivity with regions in the dorsal attention and salience networks. Optimizing the delineation of the human homologues of MEC and LEC with a combined, cross-validated DTI-fMRI approach allows to define a likely border between the two subdivisions and has implications for both cognitive and translational neuroscience research.

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Parallel cognitive maps for short-term statistical and long-term semantic relationships in the hippocampal formation

The hippocampal-entorhinal system uses cognitive maps to represent spatial knowledge and other types of relational information, such as the transition probabilities between objects. However, objects can often be characterized in terms of different types of relations simultaneously, e.g. semantic similarities learned over the course of a lifetime as well as transitions experienced over a brief timeframe in an experimental setting. Here we ask how the hippocampal formation handles the embedding of stimuli in multiple relational structures that differ vastly in terms of their mode and timescale of acquisition: Does it integrate the different stimulus dimensions into one conjunctive map, or is each dimension represented in a parallel map? To this end, we reanalyzed functional magnetic resonance imaging (fMRI) data from Garvert et al. (2017) that had previously revealed an entorhinal map which coded for newly learnt statistical regularities. We used a triplet odd-one-out task to construct a semantic distance matrix for presented items and applied fMRI adaptation analysis to show that the degree of similarity of representations in bilateral hippocampus decreases as a function of semantic distance between presented objects. Importantly, while both maps localize to the hippocampal formation, this semantic map is anatomically distinct from the originally described entorhinal map. This finding supports the idea that the hippocampal-entorhinal system forms parallel cognitive maps reflecting the embedding of objects in diverse relational structures.

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Saccades are coordinated with directed circuit dynamics and stable but distinct hippocampal patterns that promote memory formation

During natural viewing, humans explore their environment by moving the eyes - a process that involves saccades to guide attention and shape memory. Saccades are controlled by visuo-oculomotor regions and are known to impact medial temporal lobe processing, but the circuit dynamics in humans are unclear. Here, we asked which of the functional routes between the visual cortex, frontal eye fields, and the hippocampus facilitates memory encoding during visual exploration and whether saccades affect neural representations. Forty-eight human participants underwent functional magnetic resonance imaging (fMRI) and continuous monitoring of eye gaze while studying scenes and performing a recognition memory test thereafter. We discovered saccade-related excitatory coupling from the visual cortex and frontal eye fields towards the hippocampus, independent of memory. This was complemented by hippocampal inhibition of the visual cortex that determined whether participants would later remember or forget. Moreover, saccades were associated with overall stable but distinct hippocampal voxel patterns during memory formation and the degree of pattern distinctiveness positively scaled with inhibition along the hippocampus-to-visual cortex route. This suggests that eye movements are timed to the orchestration of circuit connectivity and neural representations, setting the stage for memory formation.

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Inducing a mental context for associative memory formation with real-time fMRI neurofeedback

Memory, one of the hallmarks of human cognition, can be modified when humans voluntarily modulate single neuron or neural population activity using neurofeedback. However, it is currently unknown whether memory is facilitated or impaired after such neural perturbation. In this study, participants memorized objects while we trained them with abstract neurofeedback to modulate their brain activity patterns in the ventral visual stream to represent either faces or houses. The neurofeedback created an implicit face or house context in the brain while memorizing the objects. The results revealed that participants created associations between each memorized object and its implicit context solely due to the neurofeedback manipulation. Our findings shed light onto how memory formation can be influenced by synthetic memory tags with neurofeedback and advance our understanding of mnemonic processing.

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Hippocampal spatio-temporal cognitive maps adaptively guide reward generalization

The brain forms cognitive maps of relational knowledge, an organizing principle thought to underlie our ability to generalize and make inferences. However, how can a relevant map be selected in situations where a stimulus is embedded in multiple relational structures? Here, we find that both spatial and temporal cognitive maps influence generalization in a choice task, where spatial location determines reward magnitude. Mirroring behavior, the hippocampus not only builds a map of spatial relationships but also encodes temporal distances. As the task progresses, participants choices become more influenced by spatial relationships, reflected in a strengthening of the spatial and a weakening of the temporal map. This change is driven by orbitofrontal cortex, which represents the evidence that an observed outcome is generated from the spatial rather than the temporal map and updates hippocampal representations accordingly. Taken together, this demonstrates how hippocampal cognitive maps are used and updated flexibly for inference.

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Adaptive cognitive maps for curved surfaces in the 3D world

Terrains in a 3D world can be undulating. Yet, most prior research has exclusively investigated spatial representations on a flat surface, leaving a 2D cognitive map as the dominant model in the field. Here, we investigated whether humans represent a curved surface by building a dimension-reduced flattened 2D map or a full 3D map. Participants learned the location of objects positioned on a flat and curved surface in a virtual environment by driving on the concave side of the surface (Experiment 1), driving and looking vertically (Experiment 2), or flying (Experiment 3). Subsequently, they were asked to retrieve either the path distance or the 3D Euclidean distance between the objects. Path distance estimation was good overall, but we found a significant underestimation bias for the path distance on the curve, suggesting an influence of potential 3D shortcuts, even though participants were only driving on the surface. Euclidean distance estimation was better when participants were exposed more to the global 3D structure of the environment by looking and flying. These results suggest that the representation of the 2D manifold, embedded in a 3D world, is neither purely 2D nor 3D. Rather, it is flexible and dependent on the behavioral experience and demand.

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Hippocampus and striatum encode distinct task regularities that guide human timing behavior

The brain encodes the statistical regularities of the environment in a task-specific yet flexible and generalizable format. Here, we seek to understand this process by converging two parallel lines of research, one centered on sensorimotor timing, and the other on cognitive mapping in the hippocampal system. By combining functional magnetic resonance imaging (fMRI) with a fastpaced time-to-contact (TTC) estimation task, we found that the hippocampus signaled behavioral feedback received in each trial as well as performance improvements across trials along with reward-processing regions. Critically, it signaled performance improvements independent from the tested intervals, and its activity accounted for the trial-wise regression-to-the-mean biases in TTC estimation. This suggests that the hippocampus supports the rapid encoding of temporal context even on short time scales in a behavior-dependent manner. Our results emphasize the central role of the hippocampus in statistical learning and position it at the core of a brain-wide network updating sensorimotor representations in real time for flexible behavior.

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Structural connectivity-based segmentation of the human entorhinal cortex

The medial (MEC) and lateral entorhinal cortex (LEC), widely studied in rodents, are well defined and characterized. In humans, however, the exact locations of their homologues remain uncertain. Previous functional magnetic resonance imaging (fMRI) studies have subdivided the human EC into posterior-medial (pmEC) and anterior-lateral (alEC) parts, but uncertainty remains about the choice of imaging modality and seed regions, in particular in light of a substantial revision of the classical model of EC connectivity based on novel insights from rodent anatomy. Here, we used structural, not functional imaging, namely diffusion tensor imaging (DTI) and probabilistic tractography to segment the human EC based on differential connectivity to other brain regions known to project selectively to MEC or LEC. We defined MEC as more strongly connected to presubiculum and retrosplenial cortex (RSC), and LEC as more strongly connected to distal CA1 and proximal subiculum (dCA1pSub) and orbitofrontal cortex (OFC). Although our DTI segmentation had a larger medial-lateral component than in previous fMRI studies, our results show that the human MEC and LEC homologues have a border oriented both towards the posterior-anterior and medial-lateral axes, supporting the differentiation between pmEC and alEC.

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