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

Multimodal functional and structural brain connectivity analysis in autism: A preliminary integrated approach with EEG, fMRI and DTI

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.This paper proposes a novel approach of integrating different neuroimaging techniques to characterize an autistic brain. Different techniques like EEG, fMRI and DTI have traditionally been used to find biomarkers for autism, but there have been very few attempts for a combined or multimodal approach of EEG, fMRI and DTI to understand the neurobiological basis of autism spectrum disorder (ASD). Here, we explore how the structural brain network correlate with the functional brain network, such that the information encompassed by these two could be uncovered only by using the latter. In this paper, source localization from EEG using independent component analysis (ICA) and dipole fitting has been applied first, followed by selecting those dipoles that are closest to the active regions identified with fMRI. This allows translating the high temporal resolution of EEG to estimate time varying connectivity at the spatial source level. Our analysis shows that the estimated functional connectivity between two active regions can be correlated with the physical properties of the structure obtained from DTI analysis. This constitutes a first step towards opening the possibility of using pervasive EEG to monitor the long-term impact of ASD treatment without the need for frequent expensive fMRI or DTI investigations

Spatial Representations in the Human Brain

While extensive research on the neurophysiology of spatial memory has been carried out in rodents, memory research in humans had traditionally focused on more abstract, language-based tasks. Recent studies have begun to address this gap using virtual navigation tasks in combination with electrophysiological recordings in humans. These studies suggest that the human medial temporal lobe (MTL) is equipped with a population of place and grid cells similar to that previously observed in the rodent brain. Furthermore, theta oscillations have been linked to spatial navigation and, more specifically, to the encoding and retrieval of spatial information. While some studies suggest a single navigational theta rhythm which is of lower frequency in humans than rodents, other studies advocate for the existence of two functionally distinct delta–theta frequency bands involved in both spatial and episodic memory. Despite the general consensus between rodent and human electrophysiology, behavioral work in humans does not unequivocally support the use of a metric Euclidean map for navigation. Formal models of navigational behavior, which specifically consider the spatial scale of the environment and complementary learning mechanisms, may help to better understand different navigational strategies and their neurophysiological mechanisms. Finally, the functional overlap of spatial and declarative memory in the MTL calls for a unified theory of MTL function. Such a theory will critically rely upon linking task-related phenomena at multiple temporal and spatial scales. Understanding how single cell responses relate to ongoing theta oscillations during both the encoding and retrieval of spatial and non-spatial associations appears to be key toward developing a more mechanistic understanding of memory processes in the MTL

Interactions between the hippocampus and prefrontal cortex in context-dependent overlapping memory retrieval

Activation in the hippocampus (HC) and prefrontal cortex (PFC) is critical to accurately retrieve overlapping sequences. Experiments 1 and 2 tested the hypotheses that activation in and interaction between HC and PFC increases as overlap between sequences increases in a non-spatial task. Experiment 3 tested the hypothesis that theta oscillations are involved in orchestrating interactions between HC and PFC in a spatial task with overlapping elements. In the first two studies, 17 participants (aged 18-34; 11 female) learned sequences consisting of a picture frame, face, and scene. Conditions varied by degree of overlap. Using fMRI, Experiment 1 tested how degree of overlap affected HC and PFC activation. In overlapping sequences, middle and posterior HC were active when predictability of the correct response increased, dorsolateral PFC was active when participants were able to ascertain the correct set of sequences, and ventrolateral PFC was active when inhibition of interfering associations was required. Experiment 2 examined functional connectivity of HC and PFC during disambiguation. Low- and high-overlap conditions were associated with increased connectivity in separate regions at different times indicating that retrieval under the two conditions used different neural networks and strategies. Low-overlap trials were associated with increased connectivity between HC and prefrontal and parietal regions. High-overlap trials showed increased connectivity between lateral PFC and visual areas, indicating that imagery may be necessary for accurate performance. Using EEG recording, Experiment 3 examined theta activity during retrieval of well-learned, overlapping and non-overlapping mazes in 17 participants (aged 18-34, 11 female). Theta activity increased in overlapping mazes during the first of four hallways, suggesting participants were looking ahead to upcoming turns in the maze. Theta activity increased at the beginning and choice point of the third overlapping hallway, possibly in response to interference from the paired, overlapping maze. These studies provide evidence that (1) overlapping associations in non-spatial sequences elicit interactions between hippocampus and lateral prefrontal cortex, (2) increasing the degree of overlap changes the neural processes required to perform the task, and (3) theta power increases in response to increased cognitive demand and maintenance of sequence information needed to differentiate between overlapping spatial routes

The influence of context and strategy on spatial task performance

This thesis examines naturally occurring variability in the performance of spatial tasks in order to shed light on the neurobiology that underpins human experience. It tests the theory that differences in performance of spatial tasks are an emergent property of differences in how contextual information is interpreted and the strategy implemented during task performance. Results indicate that enhanced performance accuracy in males may reflect the use of a more topographically tuned strategy rather than better spatial ability than females per se. Males and females may have different pressures leading to tendencies to rely more often on particular strategies, but this does not mean that generally one group is better than the other. Differential recruitment of lateral and medial entorhinal cortex and the nature of the information processed therein and in afferent regions of hippocampus may be what drives the differences in spatial accuracy and strategy implementation between males and females

Interaction between limbic circuits and basal ganglia in behaviour inhibition

Changing behaviour in response to changing internal and external situations is crucial for survival. In particular, we need to inhibit ongoing, unwanted or inappropriate behaviour. Behavioural inhibition includes inhibition of an ongoing action, thought or emotion (in the basal ganglia; BG). But it can also involve inhibition of goals (in the limbic system) – which is much slower. A better understanding of the neural mechanisms controlling inhibition of behaviour is important for cognitive neuroscience, particularly in relation to problems of impulsivity. This thesis aims to fill a gap in our understanding of behavioural inhibition and to elucidate the parallel circuits that control its different types. Several lesion, neuroimaging, and electrophysiological studies have been conducted to understand the role of brain regions in behavioural inhibition. Previous research has identified roles for the BG, orbitofrontal cortex (OFC) and hippocampus (HPC) in generation of various frequencies of rhythmicity during behavioural inhibition. However, the interaction between these regions has not been studied in rats during simple learning, simple action inhibition and complex behavioural inhibition. The stop signal task (SST) is the most commonly used paradigm to study simple behavioural inhibition. In this study, I recorded local field potentials (LFPs) simultaneously from BG (particularly striatum; STR and subthalamic nucleus; STN), OFC and HPC while rats performed the SST to assess how simple action inhibition differs from complex behavioural inhibition linked to goal-conflict. The data show increases in the STN LFP spectral beta power and coherence with OFC after stopping an ongoing action (simple stopping). In contrast, stop failure increased HPC-STN coherent activity in the theta frequency band. In addition to the HPC, goal-conflict also activates OFC and STN during high conflict at higher theta frequency (11-12 Hz). In contrast, the conflict induced coherence effect was seen at lower theta frequencies (5-8 Hz) between two pairs of STN (HPC-STN and OFC-STN). The results from the various experiments suggest that part of BG (STR and STN) and limbic system work in parallel and in a dynamic way for learning, response inhibition and complex behavioural inhibition (approach-avoidance conflict). The HPC is not involved in simple motor learning but may receive motivational information form STR and OFC. Simple inhibition involves mainly cortex and BG, while complex inhibition during goal-conflict also involves HPC, OFC and STN. Interestingly, goal inhibition appears to access circuits involved in simple stopping via OFC. In conclusion, functional connections between limbic and BG provides an adaptive control, so that goal selection (limbic structures) and programming of motor action (BG) can operate in parallel

Mind-Wandering Experiences in Ageing: Neurocognitive Processes and Other Influencing Factors

The ability to self-generate thoughts in imagination is a central aspect of the human experience. Mind-wandering episodes are multifaceted and are heterogeneous in terms of their content, form (e.g. modality, level of detail), and behavioural outcomes. Older adults’ neurocognitive profile shows impairments in functions highly linked to the generation and management of such episodes, namely episodic memory, attentional control, and abilities associated with the recruitment of the default mode network (DMN). Robust findings have documented a decrease in the frequency of mind-wandering with increasing age. However, age-related changes in thought content, and how this is related to the cerebral organisation of the brain, has largely been neglected. This PhD project aimed to: (i) investigate older adults’ neurocognitive profile alongside the complexities of mind-wandering, and importantly (ii) explore the impact of moderating factors on thought content as we grow older. Converging behavioural and neuroimaging methods were employed to provide a comprehensive account of self-generated thoughts. The first two chapters combined self-reports with electrophysiological and fMRI connectivity data, and demonstrated associations between changes in the recruitment of the DMN and age-related changes in self-generated thoughts. Subsequent experimental chapters considered the influence of key factors believed to impact on the content of thoughts. Examining the influence of culture revealed that native French speakers favoured self-reflection and engaged in more positively oriented thoughts, in comparison to English native speakers. In addition, the manipulation of task difficulty encouraged verbal rehearsal, and meta-awareness mainly targeted the temporal characteristics of thoughts. Finally, after a 4-week meditation intervention, there was a reduction in both negative and past-oriented thoughts. Throughout, behavioural measures demonstrated older adults’ bias toward deliberate on-task thoughts, with evidence of a decrease of negatively oriented thoughts, stable rates of positively oriented thoughts, and an increase of visual thoughts, and task-related interference. Overall, the systematic use of convergent behavioural and neuroimaging methodology has provided a more in-depth understanding of mind-wandering experiences in ageing where previously the frequency of these episodes has only been considered

Neural Correlates of Human Cognition in Real-World Environments

According to embodied accounts of human cognition, the mind is at the interface of the body and the environment. For practical reasons, however, neuroscientific research on human cognition has mostly been confined to the laboratory until now. The emergence of portable brain and body imaging research methods offers an unprecedented opportunity to capture the expression of cognitive processes during active behaviours performed in real-world contexts. In the present thesis, electroencephalography (EEG) was used to investigate embodied aspects of human cognition in motion and in the real-world. This approach, however, presents new challenges in terms of signal processing because of the increased noise related to whole body movements. As the necessary signal processing tools were not well-established, the current work involved the development of new solutions to address the specific requirements of mobile EEG data before real-world brain recordings could be validly interpreted. In a series of Event Related Potential (ERP) experiments, real-world conditions were compared to traditional lab-based conditions. The neural marker of attention (P300 ERP) was recorded when participants performed an attentional task while walking through the university’s corridors versus standing in the lab. Differences in the classic P300 ERP effect show that attentional processes in the real-world are not the same as those recorded in the lab. Following up on this finding, the attenuation of the P300 effect under real-world conditions was shown to be driven by cognitive demands related to displacement through space rather than the act of walking itself. This is a demonstration, at a brain level, that when walking in the real-world, cognitive resources are reallocated to the processing of visual flow and vestibular information associated with displacement. The findings reflect the dynamic interplay between mind, body, and environment, providing innovative evidence strengthening the embodied framework of human cognition. The same dynamic interplay between body, environment and cognitive function is uniquely represented in real-world navigation. The literature on spatial navigation in humans, however, mainly involved navigating virtual reality environments often while lying on a scanner bed. Most of the evidence on the neural markers of spatial navigation comes from intracranially recorded brain oscillations in rodents. The innovation in this thesis was to investigate brain oscillations associated with cognitive function underlying real-world navigation in humans using surface electrodes. The present work demonstrates that human brain dynamics related to navigational cognitive processes can be recorded in active exploration of real-world environments. The key finding resulting from this novel approach is that real-world spatial navigation is associated with specific neural signatures underlying distinct cognitive functions. Frontal low-frequency oscillations were found to be associated with wayfinding, while parietal high-frequency oscillations were associated with spatial memory. Furthermore, these neural correlates were found to be dynamically modulated depending on the body’s contextual positioning within the environment. Therefore, these findings again provide evidence in support of the embodiment theory of cognition. The final study addressed the concern that findings might reflect walking speed variation. The existing animal literature has shown that low-frequency bands are modulated by walking speed. This study characterised the specific modulations in spectral power as a function of walking speed in humans. Critically the pattern showed no similarity to the spectral patterns found in relation to real-world spatial navigation, confirming the cognitive interpretation of this work. Taken together, these findings provide innovative real-world evidence supporting the theoretical embodiment framework. The neural correlates of attention, memory, and spatial navigation were found to be modulated by the dynamic experience of one’s environment. Beyond this work’s theoretical implications for cognitive sciences, the present findings offer new perspectives for real-world application