Imaging the human hippocampus with optically-pumped magnetoencephalography

Optically-pumped (OP) magnetometers allow magnetoencephalography (MEG) to be performed while a participant’s head is unconstrained. To fully leverage this new technology, and in particular its capacity for mobility, the activity of deep brain structures which facilitate explorative behaviours such as navigation, must be detectable using OP-MEG. One such crucial brain region is the hippocampus. Here we had three healthy adult participants perform a hippocampal-dependent task – the imagination of novel scene imagery – while being scanned using OPMEG. A conjunction analysis across these three participants revealed a significant change in theta power in the medial temporal lobe. The peak of this activated cluster was located in the anterior hippocampus. We repeated the experiment with the same participants in a conventional SQUID-MEG scanner and found similar engagement of the medial temporal lobe, also with a peak in the anterior hippocampus. These OP-MEG findings indicate exciting new opportunities for investigating the neural correlates of a range of crucial cognitive functions in naturalistic contexts including spatial navigation, episodic memory and social interactions

The spectro-contextual encoding and retrieval theory of episodic memory.

The spectral fingerprint hypothesis, which posits that different frequencies of oscillations underlie different cognitive operations, provides one account for how interactions between brain regions support perceptual and attentive processes (Siegel etal., 2012). Here, we explore and extend this idea to the domain of human episodic memory encoding and retrieval. Incorporating findings from the synaptic to cognitive levels of organization, we argue that spectrally precise cross-frequency coupling and phase-synchronization promote the formation of hippocampal-neocortical cell assemblies that form the basis for episodic memory. We suggest that both cell assembly firing patterns as well as the global pattern of brain oscillatory activity within hippocampal-neocortical networks represents the contents of a particular memory. Drawing upon the ideas of context reinstatement and multiple trace theory, we argue that memory retrieval is driven by internal and/or external factors which recreate these frequency-specific oscillatory patterns which occur during episodic encoding. These ideas are synthesized into a novel model of episodic memory (the spectro-contextual encoding and retrieval theory, or "SCERT") that provides several testable predictions for future research

Theta phase synchronization between the human hippocampus and prefrontal cortex increases during encoding of unexpected information: A case study

Events that violate predictions are thought to not only modulate activity within the hippocampus and PFC but also enhance communication between the two regions. Scalp and intracranial EEG studies have shown that oscillations in the theta frequency band are enhanced during processing of contextually unexpected information. Some theories suggest that the hippocampus and PFC interact during processing of unexpected events, and it is possible that theta oscillations may mediate these interactions. Here, we had the rare opportunity to conduct simultaneous electrophysiological recordings from the human hippocampus and PFC from two patients undergoing presurgical evaluation for pharmacoresistant epilepsy. Recordings were conducted during a task that involved encoding of contextually expected and unexpected visual stimuli. Across both patients, hippocampal–prefrontal theta phase synchronization was significantly higher during encoding of contextually unexpected study items, relative to contextually expected study items. Furthermore, the hippocampal–prefrontal theta phase synchronization was larger for contextually unexpected items that were later remembered compared with later forgotten items. Moreover, we did not find increased theta synchronization between the PFC and rhinal cortex, suggesting that the observed effects were specific to prefrontal–hippocampal interactions. Our findings are consistent with the idea that theta oscillations orchestrate communication between the hippocampus and PFC in support of enhanced encoding of contextually deviant information

Distinct contributions of the fornix and inferior longitudinal fasciculus to episodic and semantic autobiographical memory

Autobiographical memory (AM) is multifaceted, incorporating the vivid retrieval of contextual detail (episodic AM), together with semantic knowledge that infuses meaning and coherence into past events (semantic AM). While neuropsychological evidence highlights a role for the hippocampus and anterior temporal lobe (ATL) in episodic and semantic AM, respectively, it is unclear whether these constitute dissociable large-scale AM networks. We used high angular resolution diffusion-weighted imaging and constrained spherical deconvolution-based tractography to assess white matter microstructure in 27 healthy young adult participants who were asked to recall past experiences using word cues. Inter-individual variation in the microstructure of the fornix (the main hippocampal input/output pathway) related to the amount of episodic, but not semantic, detail in AMs e independent of memory age. Conversely, microstructure of the inferior longitudinal fasciculus, linking occipitotemporal regions with ATL, correlated with semantic, but not episodic, AMs. Further, these significant correlations remained when controlling for hippocampal and ATL grey matter volume, respectively. This striking correlational double dissociation supports the view that distinct, large-scale distributed brain circuits underpin context and concepts in AM

Comparing and contrasting the cognitive effects of hippocampal and ventromedial prefrontal cortex damage: A review of human lesion studies.

The hippocampus and ventromedial prefrontal cortex (vmPFC) are closely connected brain regions whose functions are still debated. In order to offer a fresh perspective on understanding the contributions of these two brain regions to cognition, in this review we considered cognitive tasks that usually elicit deficits in hippocampal-damaged patients (e.g., autobiographical memory retrieval), and examined the performance of vmPFC-lesioned patients on these tasks. We then took cognitive tasks where performance is typically compromised following vmPFC damage (e.g., decision making), and looked at how these are affected by hippocampal lesions. Three salient motifs emerged. First, there are surprising gaps in our knowledge about how hippocampal and vmPFC patients perform on tasks typically associated with the other group. Second, while hippocampal or vmPFC damage seems to adversely affect performance on so-called hippocampal tasks, the performance of hippocampal and vmPFC patients clearly diverges on classic vmPFC tasks. Third, although performance appears analogous on hippocampal tasks, on closer inspection, there are significant disparities between hippocampal and vmPFC patients. Based on these findings, we suggest a tentative hierarchical model to explain the functions of the hippocampus and vmPFC. We propose that the vmPFC initiates the construction of mental scenes by coordinating the curation of relevant elements from neocortical areas, which are then funneled into the hippocampus to build a scene. The vmPFC then engages in iterative re-initiation via feedback loops with neocortex and hippocampus to facilitate the flow and integration of the multiple scenes that comprise the coherent unfolding of an extended mental event

Direct Stimulation of Human Hippocampus During Verbal Associative Encoding Enhances Subsequent Memory Recollection

Previous studies have reported conflicting results regarding the effect of direct electrical stimulation of the human hippocampus on memory performance. A major function of the hippocampus is to form associations between individual elements of experience. However, the effect of direct hippocampal stimulation on associative memory remains largely inconclusive, with most evidence coming from studies employing non-invasive stimulation. Here, we therefore tested the hypothesis that direct electrical stimulation of the hippocampus specifically enhances hippocampal-dependent associative memory. To test this hypothesis, we recruited surgical patients with implanted subdural electrodes to perform a word pair memory task during which the hippocampus was stimulated. Our results indicate that stimulation of the hippocampus during encoding helped to build strong associative memories and enhanced recollection in subsequent trials. Moreover, stimulation significantly increased theta power in the lateral middle temporal cortex during successful memory encoding. Overall, our findings indicate that hippocampal stimulation positively impacts performance during a word pair memory task, suggesting that successful memory encoding involves the temporal cortex, which may act together with the hippocampus

Medial prefrontal-medial temporal theta phase coupling in dynamic spatial imagery

Hippocampal–medial prefrontal interactions are thought to play a crucial role in mental simulation. Notably, the frontal midline/medial pFC (mPFC) theta rhythm in humans has been linked to introspective thought and working memory. In parallel, theta rhythms have been proposed to coordinate processing in the medial temporal cortex, retrosplenial cortex (RSc), and parietal cortex during the movement of viewpoint in imagery, extending their association with physical movement in rodent models. Here, we used noninvasive whole-head MEG to investigate theta oscillatory power and phase-locking during the 18-sec postencoding delay period of a spatial working memory task, in which participants imagined previously learned object sequences either on a blank background (object maintenance), from a first-person viewpoint in a scene (static imagery), or moving along a path past the objects (dynamic imagery). We found increases in 4- to 7-Hz theta power in mPFC when comparing the delay period with a preencoding baseline. We then examined whether the mPFC theta rhythm was phase-coupled with ongoing theta oscillations elsewhere in the brain. The same mPFC region showed significantly higher theta phase coupling with the posterior medial temporal lobe/RSc for dynamic imagery versus either object maintenance or static imagery. mPFC theta phase coupling was not observed with any other brain region. These results implicate oscillatory coupling between mPFC and medial temporal lobe/RSc theta rhythms in the dynamic mental exploration of imagined scenes

Building Mental Experiences: From Scenes to Events

Mental events are central to everyday cognition, be it our continuous perception of the world, recalling autobiographical memories, or imagining the future. Little is known about the fine-grained temporal dynamics of these processes. Given the apparent predominance of scene imagery across cognition, in this thesis I used magnetoencephalography to investigate whether and how activity in the hippocampus and ventromedial prefrontal cortex (vmPFC) supports the mental construction of scenes and the events to which they give rise. In the first experiment, participants gradually imagined scenes and also closely matched non-scene arrays; this allowed me to assess whether any brain regions showed preferential responses to scene imagery. The anterior hippocampus and vmPFC were particularly engaged by the construction of scene imagery, with the vmPFC driving hippocampal activity. In the second experiment, I found that certain objects – those that were space-defining – preferentially engaged the vmPFC and superior temporal gyrus during scene construction, providing insight into how objects affect the creation of scene representations. The third experiment involved boundary extension during scene perception, permitting me to examine how single scenes might be prepared for inclusion into events. I observed changes in evoked responses just 12.5-58 ms after scene onset over fronto-temporal sensors, with again the vmPFC exerting a driving influence on other brain regions, including the hippocampus. In the final experiment, participants watched brief movies of events built from a series of scenes or non-scene patterns. A difference in evoked responses between the two event types emerged during the first frame of the movies, the primary source of which was shown to be the hippocampus. The enduring theme of the results across experiments was scene-specific engagement of the hippocampus and vmPFC, with the latter being the driving influence. Overall, this thesis provides insights into the neural dynamics of how scenes are built, made ready for inclusion into unfolding mental episodes, and then linked to produce our seamless experience of the world

Theta and alpha oscillations as signatures of internal and external attention to delayed intentions: A magnetoencephalography (MEG) study

Abstract Background Remembering to execute delayed intentions (i.e., prospective memory, PM) entails the allocation of internal and external attention. These processes are crucial for rehearsing PM intentions in memory and for monitoring the presence of the PM cue in the environment, respectively. Aim The study took advantage of the excellent spatial and temporal resolution of magnetoencephalography (MEG) to delineate the neural mechanisms of such memory and monitoring processes underlying PM. Method The spatio-temporal dynamic of theta and alpha oscillations were explored in 21 participants in 2 p.m. tasks and compared respect to a baseline condition (i.e., a lexical decision task with no PM instruction). The PM tasks varied for the load of internally-directed attention (Retrospective-load task) vs externally-directed attention (Monitoring-load task). Results Increase in theta activity was observed in the Retrospective-load task, and was particularly expressed in the regions of the Default Mode Network, such as in medial temporal regions, precuneus, posterior cingulate cortex and medial prefrontal cortex. By contrast, alpha decrease was the most relevant feature of the Monitoring-load task, and it was expressed over bilateral occipital, occipito-parietal and fronto-temporal regions, as well as over left dorsal fronto-parietal regions. Conclusions Theta and alpha oscillations are strictly associated with the direction of attention during the PM tasks. In particular, the theta increase is linked to internal attention necessary for maintaining the intention active in working memory, whereas the alpha decrease supports the external attention for detecting the PM cue in the environment