Entorhinal and hippocampal subregions form a critical functional circuitry that binds cortical information into cohesive representations (Eichenbaum et al., 2007; Ritchey et al., 2015). The interaction of the entorhinal-hippocampal circuitry with large-scale cortical information streams and the circuitry’s inner communication are key to the formation of these cohesive representations. Here, we advance insight into how the human entorhinal cortex (EC) receives information from cortical streams and how information proceeds between the EC and the transversal axis of hippocampal subiculum and CA1 (here referred to as transversal sub/CA1 axis). These insights are relevant to our understanding of the circuitry’s fundamental role in cognitive functions such as episodic memory.

Large-scale cortical information streams, that originate in the visual ‘Where’ and ‘What’ pathways and process scene and object information (Berron et al., 2018; Haxby et al., 1991; Ranganath and Ritchey, 2012; Ritchey et al., 2015; Ungerleider and Haxby, 1994), map onto the EC in a complex manner and define functional EC subregions. [Note, in light of confusing nomenclature, here we adhere to scene and object information - elsewhere referred to as contextual, spatial or "Where" and content, non-spatial, item or "What" information, respectively.] Recent rodent research updates the former conception of a parallel mapping of scene and object information via parahippocampal and perirhinal cortices onto medial versus lateral EC subregions (cf. posterior-medial versus anterior-lateral EC subregions as the human homologues; Maass et al., 2015; Navarro Schröder et al., 2015). Instead of a strict parallel mapping, profound cross-projections exist from the parahippocampal cortex towards the perirhinal cortex and the lateral EC (Nilssen et al., 2019). In accordance, information seems to converge in the rodent lateral EC (Doan et al., 2019). The update, thus, implies a more complex functional organization than parallel scene and object information mapping. Moreover, this advance highlights the retrosplenial cortex as an additional source to convey information directly from the cortical scene processing stream onto the EC. The retrosplenial cortex projects to the medial EC and, like the parahippocampal cortex, is part of the scene processing stream (e.g. involved in scene translation; Vann et al., 2009; Nilssen et al., 2019; Witter et al., 2017). The update, furthermore, evokes the question how cortical sources of information uniquely map onto the EC and which kind of information is processed in the resulting functional EC subregions.

Within the entorhinal-hippocampal circuitry, an important direct way of communication exists between the EC and hippocampal subiculum and CA1. How functional EC subregions communicate towards the transversal sub/CA1 axis in humans is, however, unclear. Similarly, the extent to which specific scene and object information processing routes might emerge, despite information convergence in the EC, is unknown. On one hand, rodent research indicates a transversal organization where scene and object information is processed along two anatomically wired routes, the medial EC – distal subiculum – proximal CA1 route and the lateral EC – proximal subiculum – distal CA1 route, respectively (Witter et al., 2017; note sparse functional evidence in the subiculum: Ku et al., 2017; Cembrowski et al., 2018; but frequent reports in the rodent CA1 region: Henriksen et al., 2010; Nakamura et al., 2013; Igarashi et al., 2014; Nakazawa et al., 2016; Beer et al., 2018). Initial functional and structural connectivity data also indicate such a transversal connectivity profile in humans (Maass et al., 2015; Syversen et al., 2021). In accordance, scene information seems to be preferentially processed in the distal subiculum (Dalton et al., 2018; Dalton and Maguire, 2017; Zeidman et al., 2015) and hints exist for preferential object processing at the subiculum/CA1 border (Dalton et al., 2018). On the other hand, anatomical projections in the monkey show a longitudinal profile on top of the transversal profile with mainly the anterior-lateral and posterior-lateral entorhinal portions projecting to the distal subiculum – proximal CA1 and proximal subiculum – distal CA1, respectively (Witter and Amaral, 2020). According to information convergence in the EC, a recent report finds convergence along the rodent transversal CA1 axis (Vandrey et al., 2021). In humans, visual stream projections towards the entorhinal-hippocampal circuitry similarly suggest convergence of scene and object information in the subiculum/CA1 border region but preserved scene processing in the distal subiculum (Dalton and Maguire, 2017). A detailed examination of the latter hypothesis is, however, lacking. The diversity of findings emerging from the literature calls for a thorough investigation to elucidate whether multiple transversal processing routes exist within the human entorhinal-hippocampal circuitry.

To summarize, our conception of how information travels towards the entorhinal-hippocampal circuitry underwent key changes which warrant an extensive exploration of the circuitry’s functional organization. First, rodent research shows that there is no strict parallel mapping of cortical information from the perirhinal and parahippocampal cortex towards the EC. Second, information seems to converge already before the hippocampus. These changes add to several knowledge gaps. First, it is unclear in which subregions of the entorhinal-hippocampal circuitry scene and object information are processed. The general connectivity patterns in the human entorhinal-hippocampal circuitry have not yet been directly related to information processing. Moreover, it is unclear how scene information from the retrosplenial cortex maps onto the human EC as a critical source of the cortical scene processing stream. Hence, it is also unclear how retrosplenial information is communicated between the EC and the hippocampus. Finally, it remains elusive whether a transversal functional segregation can be extended towards the human CA1 region in analogy to the rodent literature.

Here, we leverage ultra-high field 7 Tesla functional imaging (fMRI) data and advance the earlier findings on human entorhinal subregions and a transversal intrinsic functional connectivity pattern in the subiculum (Maass et al., 2015). With a combination of functional connectivity and information processing analyses, we seek to answer two sets of questions. Regarding functional connectivity, we ask where the parahippocampal, perirhinal, and retrosplenial cortical sources uniquely map onto the human EC and how these functionally connected routes continue between EC subregions and the transversal sub/CA1 axis. Regarding information processing, we ask whether and where scene and object information are specifically processed in the EC and along the transversal sub/CA1 axis. We test the hypotheses of (1) a transversal functional connectivity pattern and (2) multiple information processing routes within the entorhinal-hippocampal circuitry. Thus, following the updated conception of a non-parallel cortical scene and object information mapping onto the EC in rodents, we will show how cortical information streams map onto the EC in humans. This mapping will then be our detailed starting point to investigate the functional connectivity and information processing within the entorhinal-hippocampal circuitry.

We seek to comprehensively investigate functional connectivity within the entorhinal-hippocampal circuitry and the contribution of cortical scene and object information processing streams. In an initial step, we identified where cortical sources map uniquely onto the entorhinal cortex (building upon Maass et al., 2015). The identified entorhinal subregions are based on their voxel’s preferred intrinsic functional connectivity with the retrosplenial cortex, parahippocampal cortex, perirhinal Area 35 or Area 36 regions (‘sources’). Note, that we evaluate both perirhinal subregions, Area 35 and Area 36 as separate sources as accumulating evidence suggests their structural and functional distinction (e.g. Berron et al., 2021; Burwell, 2000; Suzuki and Naya, 2014; van Strien et al., 2009). Next, we evaluated the continuation of the functional connectivity streams within the entorhinal-hippocampal circuitry and examined the intrinsic functional connectivity pattern between the identified entorhinal subregions (‘seeds’) and hippocampal subiculum and CA1 in the hippocampal body. Therefore, temporal fluctuations of BOLD signal were correlated in a seed-to-voxel manner within each participant. The resulting statistical correlational maps were aligned between participants. Repeated measures ANOVAs were calculated on connectivity preferences with seeds and transversal segments as factors to determine statistical differences in connectivity topography. All functional connectivity analyses were performed on the dataset after task-related effects have been regressed out, creating a dataset that resembles resting-state data (Gavrilescu et al., 2008; Maass et al., 2015).

Finally, we identified the corresponding bias in scene (here operationalized with room stimuli) and object information processing within entorhinal subregions and along the transversal sub/CA1 axis using the same dataset. Therefore, we extracted parameter estimates from a mnemonic discrimination task with scene and object conditions from aligned statistical maps across participants. Repeated measures ANOVAs were calculated on parameter estimates in entorhinal subregions and transversal sub/CA1 segments to determine biases in information processing within the entorhinal-hippocampal circuitry.

In the following, we first describe the four obtained entorhinal seeds and display the intrinsic functional connectivity pattern with the entorhinal seed regions along the transversal sub/CA1 axis. Thereafter, we report the information processing characteristics of the entorhinal and hippocampal subregions. Note that all results have been obtained with independent analyses in the left and right hemispheres. The largely similar left hemisphere results can be found in appendix 1. Source data and statistical maps are provided under Grande, X., Berron, D. (2022). Open Science Framework. ID 9v3qp. Source Data from Functional Connectivity and Information Processing in the Entorhinal-Hippocampal Circuitry. https://osf.io/9v3qp.

Four cortical sources divide the EC in retrosplenial-, parahippocampal, Area 35- and Area 36-based seeds

The four entorhinal subregions that we later used as seeds to determine the topography of entorhinal-hippocampal connectivity are based on intrinsic functional connectivity preferences with either the parahippocampal cortex, the retrosplenial cortex, perirhinal Area 36 or Area 35. These cortical regions are in general concordance with Maass et al., 2015 but consider recent advances that put forward the retrosplenial cortex as a critical source from the cortical scene processing stream (Nilssen et al., 2019) and evaluate perirhinal Area 35 and 36 separately.

Based on functional connectivity preferences with the four sources - parahippocampal cortex (Source code 8), retrosplenial cortex (Source code 7, Area 36 (Source code 6), and Area 35 (Source code 5) - we obtained four entorhinal seeds. The seeds refer to different parts of the EC whose voxels expressed preferential functional connectivity to either cortical source. For the EC_PHC-based seed, the majority of voxels can roughly be described as clustering in the posterior-medial entorhinal portion, for the EC_RSC-based seed in the anterior-medial portion, for the EC_Area35-based seed in the anterior-lateral portion and for the EC_Area36-based seed in the posterior-lateral entorhinal portion (see appendix 2 for exact voxel counts). Note that both perirhinal-based entorhinal seeds extended along the anterior to posterior axis such that the EC_Area35-based progressed more along the outer EC (i.e. laterally, with a main focus anteriorly) and the EC_Area36-based along the inner EC (i.e. medially, with a main focus posteriorly, see Figure 1 and the medial reflection of the EC seeds). It is important to note that these are rough qualitative descriptions of the main clusters, without quantification or an established relationship to coherent cytoarchitectonic regions. We will therefore continue to refer to them as EC_RSC-based, EC_PHC-based, EC_Area35-based and EC_Area36-based seeds.

Figure 1

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Distal subiculum is functionally connected with the EC_PHC-based seed while the subiculum/CA1 border is connected with EC_RSC-based and EC_Area35-based seeds

Following the characterization of entorhinal seeds, we focused on the functional connectivity between these entorhinal subregions and hippocampal subiculum and CA1 to test the hypothesis of a transversal functional connectivity pattern. We predicted that while some EC subregions have a preference to functionally connect with the subiculum/CA1 border, others preferentially connect with the distal subiculum and proximal CA1. In the previous step, we identified EC subregions based on unique cortical source contributions. Therefore, our predictions remained in accordance with Maass et al., 2015: We expected that the EC subregion preferentially connected with the parahippocampal cortex (EC_PHC-based seed) maps towards the distal subiculum and EC subregions connected with the perirhinal cortex (EC_Area35-based seed, EC_Area36-based seed) map towards the proximal subiculum, a mapping that we predicted to be extended towards the distal CA1.

When extracting estimates of connectivity preferences across individuals from proximal and distal hippocampal subfield segments for either entorhinal seed, repeated measures ANOVAs revealed significant seed X segments interaction effects along the transversal sub/CA1 axis (see Figure 2; subiculum: F(12,372) = 19.561; p<0.001; CA1: F(6,186) = 3.212; p=0.024).

Figure 2

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Figure 2—source data 1

Individual functional connectivity estimates to right entorhinal seeds, extracted from right subiculum and CA1 transversal segments.

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In the subiculum, additional repeated measures ANOVAs showed that the EC_Area35-based (F(4,124) = 8.913; p_FDR <0.001), EC_RSC-based (F(4,124) = 10.538; p_FDR <0.001) and EC_PHC-based (F(4,124) = 42.201; p_FDR <0.001) seeds displayed a significant main effect across the transversal subiculum segments. These differential functional connectivity preferences across the transversal axis of the subiculum interacted significantly in a subsequent repeated measures ANOVA (EC_PHC-based versus EC_RSC-based seed preference interaction: F(4,124) = 46.452; p_FDR <0.001; EC_PHC-based versus EC_Area35-based seed preference interaction: F(4,124) = 35.208; p_FDR <0.001). This pattern provides statistical evidence for an increase in preferential functional connectivity with the EC_PHC-based seed towards the distal portion of the subiculum while the preferential functional connectivity with the EC_Area35-based as well as the EC_RSC-based seeds rather increased towards the proximal portion of the subiculum.

In hippocampal CA1, additional repeated measures ANOVAs showed that the connectivity preference towards the EC_RSC-based seed displays a significant main effect across the transversal axis of CA1 (F(2,62) = 10.489; p_FDR <0.001). In distal CA1, the preferential functional connectivity with the EC_RSC-based seed was higher than in the proximal portion of CA1. In right CA1, a similar but weaker transversal pattern was observed for connectivity preferences with the EC_Area35-based (F(2,62) = 4.146; p_FDR = 0.041; note in the left hemisphere a comparable transversal pattern was observed for the EC_PHC-based and EC_RSC-based portions, see appendix 1).

Thus, in the entorhinal-hippocampal circuitry, voxels in the distal subiculum were preferentially functionally connected with the EC_PHC-based portion whereas voxels in the subiculum/CA1 border were preferentially connected with more anterior EC portions (EC_RSC-based and EC_Area35-based).

Distal subiculum and EC_PHC-based exhibit higher functional activity in the scene condition while other subregions show no significant difference between conditions

Besides the intrinsic functional connectivity patterns within the entorhinal-hippocampal circuitry, we also examined the characteristics of scene and object information processing to test the hypothesis of multiple information processing routes within the entorhinal-hippocampal circuitry. We predicted a route of specific scene processing and another route of convergent information processing. Following the proposal by Dalton and Maguire, 2017 and the updated cross-projections from the scene to the object information processing stream (Nilssen et al., 2019), we expected scene processing in the distal subiculum. The updated parahippocampal cross-projections imply convergence wherever specific object processing had been expected previously. Thus, we explored whether any entorhinal-hippocampal subregions still process object information specifically. However, we largely expected to find evidence consistent with convergent processing of scene and object information within the entorhinal-hippocampal circuitry.

We first focused on the entorhinal seed regions. When extracting task-related parameter estimates from object and scene conditions, a repeated measures ANOVA showed a significant interaction between region and information type (object versus scene, F(3,93) = 20.9267; p<0.001). Post-hoc t-tests revealed that only in the EC_PHC-based seed region functional activity in the scene condition was significantly higher than in the object condition (p_FDR<0.001), while in the remaining three entorhinal seed regions no significant difference between scene and object conditions existed (EC_Area35-based: p_FDR = 0.9129; EC_Area36-based: p_FDR = 0.9129; EC_RSC-based: p_FDR = 0.5646; see Figure 3).

Figure 3

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Figure 3—source data 1

Individual paramenter estimates for scene and object processing in right entorhinal seed regions.

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When extracting task-related parameter estimates for scene and object conditions from proximal and distal segments of hippocampal subregions within each participant, we found a significant interaction between transversal segments and information type only in the subiculum (F(4,124) = 15.994; p<0.001) and not in CA1 (F(2,62) = 2.553; p = 0.105) as revealed by repeated measures ANOVAs. Post-hoc T-tests showed significantly higher functional activity in the scene than object condition (both p_FDR <0.001) only in the distal subiculum segments. In all other segments along the subiculum transversal axis, there was no significant difference in functional activity related to scene and object conditions (all p_FDR = 0.1222; see Figure 4).

Figure 4

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Figure 4—source data 1

Individual parameter estimates for scene and object processing in right transversal subiculum and CA1 segments.

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This study aims to advance insight into the organizational principles of information processing within the entorhinal-hippocampal circuitry and the circuitry’s embedding in designated cortical processing streams. Leveraging ultra-high field 7 Tesla fMRI, we find a resemblance between the intrinsic functional connectivity pattern and subregional biases in scene information processing in the entorhinal-hippocampal circuitry. In the EC, we observe a topographical mapping of regions from the cortical scene and object information processing streams, including the retrosplenial, parahippocampal and perirhinal Area 35 and Area 36 cortices. This mapping continues to determine a transversal organization of information processing routes between the EC and the human hippocampal circuitry. Our results unify previous evidence and uncover novel features in the human brain that can be a window into the circuitry’s critical role in memory function and decline.

Relevance of the current findings for the functional organization of the entorhinal-hippocampal circuitry

The current findings (summarized in Figure 5) advance our insight into the organization of the entorhinal-hippocampal circuitry on multiple levels and contribute to cognitive and clinical research. Recent efforts to understand how the human entorhinal-hippocampal circuitry accomplishes conjunction and segregation of information largely focused on the longitudinal hippocampal axis (e.g. Brunec et al., 2018; Brunec et al., 2020; Robin and Moscovitch, 2017). The transversal axis of the hippocampus has been approached by studies in humans that did not directly relate connectivity findings to information processing and did not assess subfield-specific organization (Vos de Wael et al., 2018; Plachti et al., 2019; Kharabian Masouleh et al., 2020; Paquola et al., 2020; Bouffard et al., 2022; for an overview see Genon et al., 2021). Dalton and Maguire, 2017, however, made a relevant proposal based on visual processing pathways and information processing. In correspondence to our results, they proposed the subiculum/CA1 border as a point of convergence between scene and object information processing streams. While their conclusion was based on direct parahippocampal, retrosplenial and perirhinal connections to the hippocampus, we found that both, the EC_Area35-based (that is connected with the cortical object processing stream) and the EC_RSC-based (that is connected with the cortical scene processing stream) show connectivity with the subiculum/CA1 border (see also appendix V for information processing in cortical source regions). Convergence is potentially also achieved via recurrency within the entorhinal-hippocampal system and cortical regions (cf. Koster et al., 2018 for evidence on recurrency). These considerations are an exciting future research avenue and remain speculative based on the current data due to insufficient temporal resolution. We nevertheless hypothesize the existence of two processing routes: one that processes converged object and scene information and one that processes scene information specifically. Thus, scene and object information processing might converge before the hippocampus. This presumably occurs within the anterior EC, given object-specific and scene-specific processing take place in the cortical source regions of the EC_Area35-based and EC_RSC-based portions, respectively (see appendix 5). Here, objects may be bound together with their defining scene-like or contextual features (akin to the ‘object-in-location’ idea in Connor and Knierim, 2017; Knierim et al., 2014). In addition, the dedicated scene processing that we observe along the EC_PHC-based – distal subiculum route, may functionally underpin ideas about an anatomically graded contextual scaffold that the hippocampus utilizes to incorporate detailed information from the object-in-scene route into meaningful chunks of cohesive memory representations (‘events’; Behrens et al., 2018; Clewett et al., 2019; Robin, 2018; Robin and Olsen, 2019).

Figure 5

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For completeness, we noted differences in functional connectivity along the longitudinal axis of the subiculum. We observed, for instance, more widespread functional connectivity of the EC_Area35-based in the posterior subiculum whereas functional connectivity with the EC_PHC-based portion seems more prominent in the anterior subiculum. The latter is consistent with previous reports (Dalton et al., 2019). The former, however, needs to be explored further by taking different segmentation protocols and seed regions into account. Note, that Maass et al., 2015 did not report longitudinal differences in connectivity strength between the EC and the subiculum. Future work needs to investigate how these observations relate to the reported gradient in functional connectivity and information resolution along the hippocampal longitudinal axis (e.g. Brunec et al., 2018 but many more). Altogether, the functional organization indicates that when a memory is to be formed, some degree of information convergence happens already before the hippocampus, nevertheless keeping specific aspects of scene information separated. This conclusion is in accordance with the updated cortical mapping scheme onto the EC (Nilssen et al., 2019). The topographical specificity of our results supports the necessity of functionally assessing the entorhinal-hippocampal circuitry with high spatial resolution and investigate memory function at a subregional level (Lee et al., 2020). The features we identified can inform future hypotheses on how the hippocampus achieves the formation of cohesive representations that serve memory function.

From a clinical research perspective, it is remarkable that the current functional connectivity pattern resembles the topology of early cortical tau pathology in Alzheimer’s disease (Lace et al., 2009). An influential hypothesis suggests tau progression in Alzheimer’s disease along functionally connected pathways in the human brain (Franzmeier et al., 2020; Vogel et al., 2020). Earliest cortical tau pathology in Alzheimer’s disease accumulates in perirhinal Area 35 (also referred to as transentorhinal region) and the anterior-lateral EC before it can be found along the subiculum/CA1 border (Braak and Braak, 1995; Berron et al., 2021; Kaufman et al., 2018; Lace et al., 2009). The topology of early tau pathology in Alzheimer’s disease thus mirrors the regions that we find biased towards EC_Area35-based connectivity (Braak and Braak, 1991; Lace et al., 2009; Roussarie et al., 2020). Tau pathology in Alzheimer’s disease is associated with memory impairment (Bejanin et al., 2017; Berron et al., 2021; Nelson et al., 2012) and information processing might be affected accordingly as reports have shown an association between Alzheimer’s related tau pathology and object memory in early disease stages (Berron et al., 2019; Maass et al., 2019). However, given our finding of activity patterns consistent with object – scene convergence in those subregions of the hippocampal-entorhinal circuitry that are affected by early tau pathology, object-in-scene memory tasks might have increased sensitivity to memory impairment. Moreover, both, the entorhinal portion based on retrosplenial connectivity (EC_RSC-based) and the entorhinal portion based on Area 35 connectivity (EC_Area35-based), are functionally connected to the subiculum/CA1 border. This overlapping functional connectivity pattern in the hippocampus might be a way along which tau and amyloid pathologies in Alzheimer’s disease could interact. This is consistent with early hypometabolism and cortical tau progression in the retrosplenial cortex and early amyloid in posterior parietal regions (Grothe et al., 2017; Palmqvist et al., 2017; Ziontz et al., 2021). The revealed functional connectivity and information processing profile may guide future hypotheses on the propagation of Alzheimer’s pathology and related functional and cognitive impairment.

The current data is part of a larger study that examines exercise effects on cognition. The data that is subject to the current study have been acquired during the baseline measurement before any intervention took place. In the following, we focus on the study setup and methodological aspects of direct relevance for the current questions and data analyses.

Source data that contain numerical data used to generate Figure 2, Figure 3, Figure 4, Appendix 1 Figure 2, Appendix 1 Figure 3, Appendix 1 Figure 4, Appendix 5 Figure 1 as well as group-level statistical maps (referred to as Source Code 1-16) that underlie Figure 1, Figure 2, Appendix 1 Figure 1, Appendix 1 Figure 2, Appendix 3 Figure 1, Appendix 3 Figure 2 and Appendix 4 Figure 1 have been provided under: Open Science Framework. ID 9v3qp. https://osf.io/9v3qp.

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Author details

1. Xenia Grande

   1. Institute of Cognitive Neurology and Dementia Research, Otto von Guericke University Magdeburg, Magdeburg, Germany
   2. German Center for Neurodegenerative Diseases, Magdeburg, Germany

   Contribution

   Conceptualization, Formal analysis, Visualization, Writing - original draft, Writing – review and editing, Data Interpretation

   For correspondence

   xenia.grande@dzne.de

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0002-2486-3201

2. Magdalena M Sauvage

   1. Functional Architecture of Memory Department, Leibniz-Institute for Neurobiology, Magdeburg, Germany
   2. Functional Neuroplasticity Department, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
   3. Center for Behavioral Brain Sciences, Otto-von-Guericke University Magdeburg, Magdeburg, Germany

   Contribution

   Funding acquisition, Writing – review and editing, Data interpretation

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0002-7586-6410

3. Andreas Becke

   1. Institute of Cognitive Neurology and Dementia Research, Otto von Guericke University Magdeburg, Magdeburg, Germany
   2. German Center for Neurodegenerative Diseases, Magdeburg, Germany

   Contribution

   Investigation, Project administration

   Competing interests

   No competing interests declared

4. Emrah Düzel

   1. Institute of Cognitive Neurology and Dementia Research, Otto von Guericke University Magdeburg, Magdeburg, Germany
   2. German Center for Neurodegenerative Diseases, Magdeburg, Germany
   3. Institute of Cognitive Neuroscience, University College London, London, United Kingdom

   Contribution

   Funding acquisition, Writing – review and editing

   Competing interests

   No competing interests declared

5. David Berron

   1. German Center for Neurodegenerative Diseases, Magdeburg, Germany
   2. Center for Behavioral Brain Sciences, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
   3. Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden

   Contribution

   Conceptualization, Supervision, Funding acquisition, Investigation, Project administration, Writing – review and editing, Data Interpretation

   For correspondence

   david.berron@dzne.de

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0003-1558-1883

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