Hierarchical gradients of encoded spatial and sensory information in the neocortex are attenuated by dorsal hippocampal lesions.

During navigation, the neocortex must actively integrate learned spatial context with current sensory experience to guide behaviours. However, the relative encoding of spatial and sensorimotor information among cortical cells, and whether hippocampal feedback continues to modify these properties in familiar environments, remains poorly understood. Thus, two-photon microscopy of male and female Thy1-GCaMP6s mice was used to longitudinally image neurons spanning superficial retrosplenial cortex and layers II-Va of primary and secondary motor cortices before and after bilateral dorsal hippocampal lesions. During behaviour on a familiar cued treadmill, the locations of two added obstacles were interchanged to decouple place-tuning from cue-tuning among the position correlated cells with fields at those locations. The subpopulations of place- and cue-tuned cells each formed interareal gradients such that higher-level cortical regions exhibited higher fractions of place cells, whereas lower-level regions exhibited higher fractions of cue cells. Position correlated cells in motor cortex also formed translaminar gradients; cells closer to the cortical surface were more likely to exhibit fields and were more sparsely and precisely tuned than deeper cells. After dorsal hippocampal lesions, a neural representation of the learned environment persisted but retrosplenial cortex exhibited significantly increased cue-tuning and, in motor cortices, both position correlated cell recruitment and population activity at the unstable obstacle locations became more homogeneously elevated across laminae. Altogether, these results support that the hippocampus continues to modulate cortical responses in familiar environments, and the relative impact of top-down feedback obeys hierarchical interareal and interlaminar gradients opposite to the flow of bottom-up sensory inputs.Significance statement During learning, the hippocampus imparts spatial context to memory representations throughout the superficial neocortex. However, the post-learning role of the hippocampus has not been well defined. The results of this study suggest that, during navigation of a familiar environment, the hippocampus continues to link unreliable sensory attributes to a stable contextual framework, effectively updating the learned model of the environment. The results are also consistent with top-down suppression of sensory-evoked activity during behaviour, which varied in strength according to hierarchical proximity to the hippocampus. This effect was abolished by bilateral lesions of the dorsal hippocampus, supporting that the hippocampus plays an ongoing role in propagating context-dependent predictions throughout the cortical hierarchy, a core hypothesis of the predictive coding theoretical framework.

Inverse radon transform with deep learning: an application in cardiac motion correction.

Objective. This paper addresses performing inverse radon transform (IRT) with artificial neural network (ANN) or deep learning, simultaneously with cardiac motion correction (MC). The suggested application domain is cardiac image reconstruction in emission or transmission tomography where IRT is relevant. Our main contribution is in proposing an ANN architecture that is particularly suitable for this purpose.Approach. We validate our approach with two types of datasets. First, we use an abstract object that looks like a heart to simulate motion-blurred radon transform. With the known ground truth in hand, we then train our proposed ANN architecture and validate its effectiveness in MC. Second, we used human cardiac gated datasets for training and validation of our approach. The gating mechanism bins data over time using the electro-cardiogram (ECG) signals for cardiac motion correction.Main results. We have shown that trained ANNs can perform motion-corrected image reconstruction directly from a motion-corrupted sinogram. We have compared our model against two other known ANN-based approaches.Significance. Our method paves the way for eliminating any need for hardware gating in medical imaging.

Cortical reactivation of spatial and non-spatial features coordinates with hippocampus to form a memory dialogue.

Episodic memories comprise diverse attributes of experience distributed across neocortical areas. The hippocampus is integral to rapidly binding these diffuse representations, as they occur, to be later reinstated. However, the nature of the information exchanged during this hippocampal-cortical dialogue remains poorly understood. A recent study has shown that the secondary motor cortex carries two types of representations: place cell-like activity, which were impaired by hippocampal lesions, and responses tied to visuo-tactile cues, which became more pronounced following hippocampal lesions. Using two-photon Ca2+ imaging to record neuronal activities in the secondary motor cortex of male Thy1-GCaMP6s mice, we assessed the cortical retrieval of spatial and non-spatial attributes from previous explorations in a virtual environment. We show that, following navigation, spontaneous resting state reactivations convey varying degrees of spatial (trajectory sequences) and non-spatial (visuo-tactile attributes) information, while reactivations of non-spatial attributes tend to precede reactivations of spatial representations surrounding hippocampal sharp-wave ripples.

Weak-hyperactive hippocampal CA1 neurons in the prodromal stage of Alzheimer's disease in hybrid AppNL-G-F/NL-G-F × Thy1-GCaMP6s+/- mice suggest disrupted plasticity.

This study investigated the impact of familial Alzheimer's disease (AD)-linked amyloid precursor protein (App) mutations on hippocampal CA1 neuronal activity and function at an early disease stage in AppNL-G-F/NL-G-F × Thy1-GCaMP6s+/- (A-TG) mice using calcium imaging. Longitudinal assessment of spatial behavior at 12 and 18 months of age identified an early disease stage at 12 months when there was significant amyloid beta pathology with mild behavioral deficits. Hippocampal CA1 neuronal activity and event-related encoding of distance and time were therefore assessed at 12 months of age in several configurations of an air-induced running task to assess the dynamics of cellular activity. Neurons in A-TG mice displayed diminished (weaker) and more frequent (hyperactive) neuronal firing that was more pronounced during movement compared to immobility. Responsive neurons showed configuration-specific deficits in distance and time encoding with impairment in adapting their responses to changing configurations. These results suggest that at an early stage of AD in the absence of full-blown behavioral deficits, weak-hyperactive neuronal activity may induce impairments in sensory perception of changing environments.

Consolidation of cellular memory representations in superficial neocortex.

Systems-level memory consolidation, a key concept in memory research, involves the conversion of memories that depend on the hippocampus for their formation into efficient hippocampus-independent forms, presumably encoded by cortico-cortical connections. Yet, little is understood about the nature of consolidated neural codes at the cellular ensemble level. Mice require an intact hippocampus for "virtual" spatial learning and to develop neocortical representations of the corresponding experiences. We find that, whereas a novel virtual environment is neither learned nor represented in superficial cortex following severe damage to hippocampus, pre-operatively learned memories and their corresponding sparse and widespread neural ensemble representations in cortical layers II-III are preserved, a sine qua non of memory consolidation. These findings provide a new window for future study of the cellular mechanisms of memory consolidation.

Spatial Information Encoding across Multiple Neocortical Regions Depends on an Intact Hippocampus.

There has been considerable research showing populations of neurons encoding for different aspects of space in the brain. Recently, several studies using two-photon calcium imaging and virtual navigation have identified "spatially" modulated neurons in the posterior cortex. We enquire here whether the presence of such spatial representations may be a cortex-wide phenomenon and, if so, whether these representations can be organized in the absence of the hippocampus. To this end, we imaged the dorsal cortex of mice running on a treadmill populated with tactile cues. A high percentage (40-80%) of the detected neurons exhibited sparse, spatially localized activity, with activity fields uniformly localized over the track. The development of this location specificity was impaired by hippocampal damage. Thus, there is a substantial population of neurons distributed widely over the cortex that collectively form a continuous representation of the explored environment, and hippocampal outflow is necessary to organize this phenomenon.SIGNIFICANCE STATEMENT Increasing evidence points to the role of the neocortex in encoding spatial information. Whether this feature is linked to hippocampal functions is largely unknown. Here, we systematically surveyed multiple regions in the dorsal cortex of the same animal for the presence of signals encoding for spatial position. We described populations of cortical neurons expressing sequential patterns of activity localized in space in primary, secondary, and associational areas. Furthermore, we showed that the formation of these spatial representations was impacted by hippocampal lesion. Our results indicate that hippocampal inputs are necessary to maintain a precise cortical representation of space.

Coordinated activities of retrosplenial ensembles during resting-state encode spatial landmarks.

The brain likely uses offline periods to consolidate recent memories. One hypothesis holds that the hippocampal output provides a unique, global linking or 'index' code for each memory, and that this code is stored in the cortex in association with locally encoded attributes of each memory. Activation of the index code is hypothesized to evoke coordinated memory trace reactivation thus facilitating consolidation. Retrosplenial cortex (RSC) is a major recipient of hippocampal outflow and we have described populations of neurons there with sparse and orthogonal coding characteristics that resemble hippocampal 'place' cells, and whose expression depends on an intact hippocampus. Using two-photon Ca2+ imaging, we recorded ensembles of neurons in the RSC during periods of immobility before and after active running on a familiar linear treadmill track. Synchronous bursting of distinct groups of neurons occurred during rest both prior to and after running. In the second rest epoch, these patterns were associated with the locations of tactile landmarks and reward. Complementing established views on the functions of the RSC, our findings indicate that the structure is involved with processing landmark information during rest. This article is part of the Theo Murphy meeting issue 'Memory reactivation: replaying events past, present and future'.

Comparison of sparse domain approaches for 4D SPECT dynamic image reconstruction.

PURPOSE: Dynamic imaging (DI) provides additional diagnostic information in emission tomography in comparison to conventional static imaging at the cost of being computationally more challenging. Dynamic single photon emission computed tomography (SPECT) reconstruction is particularly difficult because of the limitations in the sampling geometry present in most existing scanners. We have developed an algorithm Spline Initialized Factor Analysis of Dynamic Structures (SIFADS) that is a matrix factorization method for reconstructing the dynamics of tracers in tissues and blood directly from the projections in dynamic cardiac SPECT, without first resorting to any 3D reconstruction. METHODS: SIFADS is different from "pure" factor analysis in dynamic structures (FADS) in that it employs a dedicated spline-based pre-initialization. In this paper, we analyze the convergence properties of SIFADS and FADS using multiple metrics. The performances of the two approaches are evaluated for numerically simulated data and for real dynamic SPECT data from canine and human subjects. RESULTS: For SIFADS, metrics analyzed for reconstruction algorithm convergence show better features of the metric curves vs iterations. In addition, SIAFDS provides better tissue segmentations than that from pure FADS. Measured computational times are also typically better for SIFADS implementations than those with pure FADS. CONCLUSION: The analysis supports the utility of the pre-initialization of a factorization algorithm for better dynamic SPECT image reconstruction.

Sparse domain approaches in dynamic SPECT imaging with high-performance computing.

Iterative reconstruction algorithms often have relatively large computation time affecting their clinical deployment. This is especially true for 4D reconstruction in dynamic imaging (DI). In this work, we have shown how sparse domain approaches and parallelization for static 3D image reconstruction and 4D dynamic image reconstruction (directly from sinogram) in Single Photon Emission Computed Tomography (SPECT), without any intermediate 3D reconstructions, can improve computational efficiency. DI in SPECT is one of the hardest inverse problems in medical image reconstruction area and slow reconstruction is a challenge for this promising protocol. Our work hopefully, paves a new direction toward making DI in SPECT clinically viable. Our 4D reconstruction also is a novel application of non-negative matrix factorization (NNMF) in an inverse problem.