An Unexpected Sequence of Events: Mismatch Detection in the Human Hippocampus

The ability to identify and react to novelty within the environment is fundamental to survival. Computational models emphasize the potential role of the hippocampus in novelty detection, its unique anatomical circuitry making it ideally suited to act as a comparator between past and present experience. The hippocampus, therefore, is viewed to detect associative mismatches between what is expected based on retrieval of past experience and current sensory input. However, direct evidence that the human hippocampus performs such operations is lacking. We explored brain responses to novel sequences of objects using functional magnetic resonance imaging (fMRI), while subjects performed an incidental target detection task. Our results demonstrate that hippocampal activation was maximal when prior predictions concerning which object would appear next in a sequence were violated by sensory reality. In so doing, we establish the biological reality of associative match-mismatch computations within the human hippocampus, a process widely held to play a cardinal role in novelty detection. Our results also suggest that the hippocampus may generate predictions about how future events will unfold, and critically detect when these expectancies are violated, even when task demands do not require it. The present study also offers broader insights into the nature of essential computations carried out by the hippocampus, which may also underpin its unique contribution to episodic memory

Neocortical Connectivity during Episodic Memory Formation

During the formation of new episodic memories, a rich array of perceptual information is bound together for long-term storage. However, the brain mechanisms by which sensory representations (such as colors, objects, or individuals) are selected for episodic encoding are currently unknown. We describe a functional magnetic resonance imaging experiment in which participants encoded the association between two classes of visual stimuli that elicit selective responses in the extrastriate visual cortex (faces and houses). Using connectivity analyses, we show that correlation in the hemodynamic signal between face- and place-sensitive voxels and the left dorsolateral prefrontal cortex is a reliable predictor of successful face–house binding. These data support the view that during episodic encoding, “top-down” control signals originating in the prefrontal cortex help determine which perceptual information is fated to be bound into the new episodic memory trace

TMS-Induced Cortical Potentiation during Wakefulness Locally Increases Slow Wave Activity during Sleep

BACKGROUND: Sleep slow wave activity (SWA) is thought to reflect sleep need, increasing in proportion to the length of prior wakefulness and decreasing during sleep. However, the process responsible for SWA regulation is not known. We showed recently that SWA increases locally after a learning task involving a circumscribed brain region, suggesting that SWA may reflect plastic changes triggered by learning. METHODOLOGY/PRINCIPAL FINDINGS: To test this hypothesis directly, we used transcranial magnetic stimulation (TMS) in conjunction with high-density EEG in humans. We show that 5-Hz TMS applied to motor cortex induces a localized potentiation of TMS-evoked cortical EEG responses. We then show that, in the sleep episode following 5-Hz TMS, SWA increases markedly (+39.1±17.4%, p<0.01, n = 10). Electrode coregistration with magnetic resonance images localized the increase in SWA to the same premotor site as the maximum TMS-induced potentiation during wakefulness. Moreover, the magnitude of potentiation during wakefulness predicts the local increase in SWA during sleep. CONCLUSIONS/SIGNIFICANCE: These results provide direct evidence for a link between plastic changes and the local regulation of sleep need

From Rapid Place Learning to Behavioral Performance: A Key Role for the Intermediate Hippocampus

Rapid place encoding by hippocampal neurons, as reflected by place-related firing, has been intensely studied, whereas the substrates that translate hippocampal place codes into behavior have received little attention. A key point relevant to this translation is that hippocampal organization is characterized by functional-anatomical gradients along the septotemporal axis: Whereas the ability of hippocampal neurons to encode accurate place information declines from the septal to temporal end, hippocampal connectivity to prefrontal and subcortical sites that might relate such place information to behavioral-control processes shows an opposite gradient. We examined in rats the impact of selective lesions to relevant parts of the hippocampus on behavioral tests requiring place learning (watermaze procedures) and on in vivo electrophysiological models of hippocampal encoding (long-term potentiation [LTP], place cells). We found that the intermediate hippocampus is necessary and largely sufficient for behavioral performance based on rapid place learning. In contrast, a residual septal pole of the hippocampus, although displaying intact electrophysiological indices of rapid information encoding (LTP, precise place-related firing, and rapid remapping), failed to sustain watermaze performance based on rapid place learning. These data highlight the important distinction between hippocampal encoding and the behavioral performance based on such encoding, and suggest that the intermediate hippocampus, where substrates of rapid accurate place encoding converge with links to behavioral control, is critical to translate rapid (one-trial) place learning into navigational performance

Event-related brain dynamics

Event-related potentials (ERPs) provide evidence of a direct link between cognitive events and brain electrical activity in a wide range of cognitive paradigms. It has generally been held that an ERP is the result of a set of discrete stimulus-evoked brain events. A recent study, however, provides new evidence to suggest that some ERP components might be generated by stimulus-induced changes in ongoing brain dynamics. This is consistent with views emerging from several neuroscientific fields, suggesting that phase synchronization of ongoing rhythms across different spatio-temporal scales mediates the functional integration necessary to perform higher cognitive tasks