The Construction of Semantic Memory: Grammar-Based Representations Learned from Relational Episodic Information

After acquisition, memories underlie a process of consolidation, making them more resistant to interference and brain injury. Memory consolidation involves systems-level interactions, most importantly between the hippocampus and associated structures, which takes part in the initial encoding of memory, and the neocortex, which supports long-term storage. This dichotomy parallels the contrast between episodic memory (tied to the hippocampal formation), collecting an autobiographical stream of experiences, and semantic memory, a repertoire of facts and statistical regularities about the world, involving the neocortex at large. Experimental evidence points to a gradual transformation of memories, following encoding, from an episodic to a semantic character. This may require an exchange of information between different memory modules during inactive periods. We propose a theory for such interactions and for the formation of semantic memory, in which episodic memory is encoded as relational data. Semantic memory is modeled as a modified stochastic grammar, which learns to parse episodic configurations expressed as an association matrix. The grammar produces tree-like representations of episodes, describing the relationships between its main constituents at multiple levels of categorization, based on its current knowledge of world regularities. These regularities are learned by the grammar from episodic memory information, through an expectation-maximization procedure, analogous to the inside–outside algorithm for stochastic context-free grammars. We propose that a Monte-Carlo sampling version of this algorithm can be mapped on the dynamics of “sleep replay” of previously acquired information in the hippocampus and neocortex. We propose that the model can reproduce several properties of semantic memory such as decontextualization, top-down processing, and creation of schemata

Powder diffraction in the range of milliseconds

Powder diffraction studies with synchrotron radiation were performed on a time scale down to 2.5 ms at the HASYLAB beamline B2 with a commercial 1024 pixel linear photodiode-array detector system (OMA III, EG&G-PARC). The flux rate of 2 x 108 photons s-1 at a wavelength of 1.26 Å achieved by using a toroidal mirror and a standard double-crystal Si(111) monochromator was measured with an ionization chamber at the focus. With a synthetic multilayer to select the desired wavelength instead of the standard monochromator, a flux rate of 1.5 x 1010 photons s-1 was measured at a wavelength of 1.31 Å. The shortest possible recording times for a complete powder pattern of calcium fluoride were 200 ms with the crystal monochromator and 2.5 ms with the multilayer. The angular resolution for both cases is discussed. The high-speed data collection was successfully applied with the double-crystal and multilayer monochromators to the recording of more-complex patterns and to monitor a phase transformation in order to demonstrate the feasibility of kinetic studies on the millisecond time scale

Multisensory task demands temporally extend the causal requirement for visual cortex in perception

Primary sensory areas constitute crucial nodes during perceptual decision making. However, it remains unclear to what extent they mainly constitute a feedforward processing step, or rather are continuously involved in a recurrent network together with higher-order areas. We found that the temporal window in which primary visual cortex is required for the detection of identical visual stimuli was extended when task demands were increased via an additional sensory modality that had to be monitored. Late-onset optogenetic inactivation preserved bottom-up, early-onset responses which faithfully encoded stimulus features, and was effective in impairing detection only if it preceded a late, report-related phase of the cortical response. Increasing task demands were marked by longer reaction times and the effect of late optogenetic inactivation scaled with reaction time. Thus, independently of visual stimulus complexity, multisensory task demands determine the temporal requirement for ongoing sensory-related activity in V1, which overlaps with report-related activity

Neural processes mediating contextual influences on human choice behaviour

Contextual influences on choice are ubiquitous in ecological settings. Current evidence suggests that subjective values are normalized with respect to the distribution of potentially available rewards. However, how this context-sensitivity is realised in the brain remains unknown. To address this, here we examine functional magnetic resonance imaging (fMRI) data during performance of a gambling task where blocks comprise values drawn from one of two different, but partially overlapping, reward distributions or contexts. At the beginning of each block (when information about context is provided), hippocampus is activated and this response is enhanced when contextual influence on choice increases. In addition, response to value in ventral tegmental area/substantia nigra (VTA/SN) shows context-sensitivity, an effect enhanced with an increased contextual influence on choice. Finally, greater response in hippocampus at block start is associated with enhanced context sensitivity in VTA/SN. These findings suggest that context-sensitive choice is driven by a brain circuit involving hippocampus and dopaminergic midbrain

Deep brain stimulation of the central thalamus restores arousal and motivation in a zolpidem-responsive patient with akinetic mutism after severe brain injury

After severe brain injury, zolpidem is known to cause spectacular, often short-lived, restorations of brain functions in a small subgroup of patients. Previously, we showed that these zolpidem-induced neurological recoveries can be paralleled by significant changes in functional connectivity throughout the brain. Deep brain stimulation (DBS) is a neurosurgical intervention known to modulate functional connectivity in a wide variety of neurological disorders. In this study, we used DBS to restore arousal and motivation in a zolpidem-responsive patient with severe brain injury and a concomitant disorder of diminished motivation, more than 10 years after surviving hypoxic ischemia. We found that DBS of the central thalamus, targeted at the centromedian-parafascicular complex, immediately restored arousal and was able to transition the patient from a state of deep sleep to full wakefulness. Moreover, DBS was associated with temporary restoration of communication and ability to walk and eat in an otherwise wheelchair-bound and mute patient. With the use of magnetoencephalography (MEG), we revealed that DBS was generally associated with a marked decrease in aberrantly high levels of functional connectivity throughout the brain, mimicking the effects of zolpidem. These results imply that 'pathological hyperconnectivity' after severe brain injury can be associated with reduced arousal and behavioral performance and that DBS is able to modulate connectivity towards a 'healthier baseline' with lower synchronization, and, can restore functional brain networks long after severe brain injury. The presence of hyperconnectivity after brain injury may be a possible future marker for a patient's responsiveness for restorative interventions, such as DBS, and suggests that lower degrees of overall brain synchronization may be conducive to cognition and behavioral responsiveness

Spike-based coupling between single neurons and populations across rat sensory cortices, perirhinal cortex, and hippocampus

Cortical computations require coordination of neuronal activity within and across multiple areas. We characterized spiking relationships within and between areas by quantifying coupling of single neurons to population firing patterns. Single-neuron population coupling (SNPC) was investigated using ensemble recordings from hippocampal CA1 region and somatosensory, visual, and perirhinal cortices. Within-area coupling was heterogeneous across structures, with area CA1 showing higher levels than neocortical regions. In contrast to known anatomical connectivity, between-area coupling showed strong firing coherence of sensory neocortices with CA1, but less with perirhinal cortex. Cells in sensory neocortices and CA1 showed positive correlations between within- and between-area coupling; these were weaker for perirhinal cortex. All four areas harbored broadcasting cells, connecting to multiple external areas, which was uncorrelated to within-area coupling strength. When examining correlations between SNPC and spatial coding, we found that, if such correlations were significant, they were negative. This result was consistent with an overall preservation of SNPC across different brain states, suggesting a strong dependence on intrinsic network connectivity. Overall, SNPC offers an important window on cell-to-population synchronization in multi-area networks. Instead of pointing to specific information-coding functions, our results indicate a primary function of SNPC in dynamically organizing communication in systems composed of multiple, interconnected areas

Neural correlates of object identity and reward outcome in the sensory cortical-hippocampal hierarchy:coding of motivational information in perirhinal cortex

Neural circuits support behavioral adaptations by integrating sensory and motor information with reward and error-driven learning signals, but it remains poorly understood how these signals are distributed across different levels of the corticohippocampal hierarchy. We trained rats on a multisensory object-recognition task and compared visual and tactile responses of simultaneously recorded neuronal ensembles in somatosensory cortex, secondary visual cortex, perirhinal cortex, and hippocampus. The sensory regions primarily represented unisensory information, whereas hippocampus was modulated by both vision and touch. Surprisingly, the sensory cortices and the hippocampus coded object-specific information, whereas the perirhinal cortex did not. Instead, perirhinal cortical neurons signaled trial outcome upon reward-based feedback. A majority of outcome-related perirhinal cells responded to a negative outcome (reward omission), whereas a minority of other cells coded positive outcome (reward delivery). Our results highlight a distributed neural coding of multisensory variables in the cortico-hippocampal hierarchy. Notably, the perirhinal cortex emerges as a crucial region for conveying motivational outcomes, whereas distinct functions related to object identity are observed in the sensory cortices and hippocampus

New technologies for examining neuronal ensembles in drug addiction and fear

Correlational data suggest that learned associations are encoded within neuronal ensembles. However, it has been difficult to prove that neuronal ensembles mediate learned behaviours because traditional pharmacological and lesion methods, and even newer cell type-specific methods, affect both activated and non-activated neurons. Additionally, previous studies on synaptic and molecular alterations induced by learning did not distinguish between behaviourally activated and non-activated neurons. Here, we describe three new approaches—Daun02 inactivation, FACS sorting of activated neurons and c-fos-GFP transgenic rats — that have been used to selectively target and study activated neuronal ensembles in models of conditioned drug effects and relapse. We also describe two new tools — c-fos-tTA mice and inactivation of CREB-overexpressing neurons — that have been used to study the role of neuronal ensembles in conditioned fear