Grid-like processing of imagined navigation

Grid cells in the entorhinal cortex (EC) of rodents [1] and humans [2] fire in a hexagonally distributed spatially periodic manner. In concert with other spatial cells in the medial temporal lobe (MTL) [3-6], they provide a representation of our location within an environment [7, 8] and are specifically thought to allow the represented location to be updated by self-motion [9]. Grid-like signals have been seen throughout the autobiographical memory system [10], suggesting a much more general role in memory [11, 12]. Grid cells may allow us to move our viewpoint in imagination [13], a useful function for goal-directed navigation and planning [12, 14-16], and episodic future thinking more generally [17, 18]. We used fMRI to provide evidence for similar grid-like signals in human entorhinal cortex during both virtual navigation and imagined navigation of the same paths. We show that this signal is present in periods of active navigation and imagination, with a similar orientation in both and with the specifically 6-fold rotational symmetry characteristic of grid cell firing. We therefore provide the first evidence suggesting that grid cells are utilized during movement of viewpoint within imagery, potentially underpinning our more general ability to mentally traverse possible routes in the service of planning and episodic future thinking

Neural representational similarity in episodic and spatial memory

Electrophysiological recordings in rodents and humans show that the contents of spatial and episodic memories are encoded in patterns of activity across neural populations. Here, I applied a mixture of univariate and multivariate techniques to functional magnetic resonance imaging (fMRI) data to investigate memory processes as well as look at how activity across voxels relates to the way memories are represented in the brain. In the first part of the thesis, I applied the Representational Similarity Analysis (RSA) to investigate the brain representations underlying spatial memories. I examined fMRI data from participants during actual or imagined navigation in virtual environments. Evidence for grid cells, one of the principal types of spatial cells, has been reported in single-cell recordings and in univariate approaches to fMRI data. I found evidence for viewing direction within occipital areas in both modalities, suggesting involvement of the same system in both tasks, but not for the six-fold symmetry characteristic of the grid cell signal. I discuss the potential reasons for this null result. In the second part I looked at episodic memories, in particular whether similar information undergoes ‘pattern separation’ during encoding to minimise future interference. I designed tasks using face morphing stimuli and multi-element events with overlapping elements to look for behavioural evidence for pattern separation and interference. The overlapping events showed increased independence in performance across multiple retrievals, suggesting the formation of more independent representations compared to unrelated events. I then looked for neural signatures of this effect using fMRI RSA. I found evidence for a decreased similarity of patterns of overlapping events at retrieval but not at encoding, possibly due to larger influence of perceptual similarity at encoding. Increased pattern separation was not related to decreased interference (improved performance). Lastly, I found evidence of non-target reinstatement, consistently with holistic representation of memory episodes. Overall, this thesis presents new findings as well as replications of previously observed effects using a range of novel behavioural and analysis techniques to investigate how spatial and episodic memories are represented in the human brain

Probabilistic atlas of the cerebellar lobules.

<p>(<b>A</b>) The compartments of the cerebellar atlas [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0133402#pone.0133402.ref016" target="_blank">16</a>] projected to the flatmap. Note that for lobule VI-X, a vermal and two hemispheric compartments (shown in slightly different colors) are defined. (<b>B</b>) The same data displayed on a posterior view of the outer surface.</p

Functional activity maps from the Human Connectome Project.

<p>(<b>A</b>) Sensorimotor topography of activation for hand, foot and tongue movements. (<b>B</b>) Working memory; contrast between a 2-back and 0-back condition. (<b>C</b>) Emotion processing; contrast between matching emotional faces vs. matching neutral shapes. (<b>D</b>) Social cognition; observing dot motion with intentional content vs. random dot motion. (<b>E</b>) Language vs. mathematical processing. Positive values indicate higher activity during processing of a story vs. arithmetic operations. Negative values represent the opposite contrast. All maps are based on N = 100 subjects. All colored areas in cognitive maps (B-E) exceed an FWE-corrected significance threshold of <i>p</i><0.05.</p

Distortion of the flatmap in representing cerebellar grey-matter volume as surface area.

<p>(<b>A</b>) Flatmap with superimposed distortion factor (ratio of Area to Volume). Orange / red areas indicate regions that are disproportionally large on the flatmap, turquoise / blue areas indicate regions that are disproportionally small. Dotted lines indicate boundaries between lobules. Thick black lines on the perimeter indicate where cuts have been made to the map. The areas connected with dashed lines are immediately adjacent in the volume, but are unfolded in the flatmap to minimize distortion. (<b>B</b>) Volume of each lobule (in % of total grey-matter volume) plotted against the corresponding area on the flatmap (in % of total map area). Plotted are 28 compartments, hemisphere and vermis of each of the main lobules, as defined in the probabilistic atlas of the human cerebellum.</p

Atlas of cerebellar-cortical connectivity.

<p>(<b>A</b>) Cortical networks of resting-state connectivity [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0133402#pone.0133402.ref023" target="_blank">23</a>]. 17 networks are shown on an inflated cortical surface of the left and right hemisphere—with both the lateral and medial surface shown. (<b>B</b>) Map showing the cortical resting-state network that correlated best with the activity in the corresponding cerebellar area [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0133402#pone.0133402.ref018" target="_blank">18</a>]. Maps are based on N = 1000 subjects.</p

Surface-based display of volume-averaged cerebellar imaging data

The paper presents a flat representation of the human cerebellum, useful for visualizing functional imaging data after volume-based normalization and averaging across subjects. Instead of reconstructing individual cerebellar surfaces, the method uses a white- and greymatter surface defined on volume-averaged anatomical data. Functional data can be projected along the lines of corresponding vertices on the two surfaces. The flat representation is optimized to yield a roughly proportional relationship between the surface area of the 2Drepresentation and the volume of the underlying cerebellar grey matter. The map allows users to visualize the activation state of the complete cerebellar grey matter in one concise view, equally revealing both the anterior-posterior (lobular) and medial-lateral organization. As examples, published data on resting-state networks and task-related activity are presented on the flatmap. The software and maps are freely available and compatible with most major neuroimaging packages. Copyright