Allocentric memory and hippocampal function

PhD ThesisApproximately one-third of trauma patients are coagulopathic on arrival to the emergency department. Acute traumatic coagulopathy and systemic inflammatory responses are serious secondary consequences of severe trauma and are linked to increased morbidity and mortality. Early tissue hypoxia is a major component in the aetiology of both complications. New resuscitation strategies are aimed at improving tissue oxygenation in the pre-hospital phase, and may attenuate coagulopathy and inflammatory sequelae. This is of particular importance in military personnel who suffer complex injuries, often from blast exposure, and may have extended evacuation times. This thesis evaluates the effect of a novel hybrid (NH) resuscitation strategy on coagulation and inflammation. Terminally anaesthetised pigs were randomised to one of two injury strands of haemorrhage +/- blast injury; initially resuscitated with 0.9% Saline to a hypotensive systolic blood pressure of 80mmHg for one hour. This was followed by either a return to a normotensive pressure (110mmHg) (NH) or a continuation at the hypotensive level. Over both injury strands NH significantly reduced Prothrombin Time, PT (mean proportion of baseline: 1.40±0.05 vs. 1.80±0.09; p=0.001) and interleukin-6 (IL6) levels (mean 1106±153 vs. 429±79 pg/ml; p=0.001) compared to the hypotensive groups. PT was positively correlated with IL6 (p=0.002) and base deficit (p=0.0004). These findings indicate that improving tissue oxygenation reduces the coagulation derangement and the pro-inflammatory response. No difference in coagulopathy was found between injury strands although blast did cause greater inflammation. Early identification of coagulopathic casualties is essential and a separate feasibility field study was preformed to assess the use of thromboelastometry in a deployed military hospital, evaluating the degree of coagulopathy in battlefield casualties and to monitor the coagulation status during the resuscitation process. In conclusion, NH attenuated the acute traumatic coagulopathy and inflammatory responses and therefore should be considered when an extended casualty evacuation is enforced

Cues, context, and long-term memory: the role of the retrosplenial cortex in spatial cognition

Spatial navigation requires representations of landmarks and other navigation cues. The retrosplenial cortex (RSC) is anatomically positioned between limbic areas important for memory formation, such as the hippocampus and the anterior thalamus, and cortical regions along the dorsal stream known to contribute importantly to long-term spatial representation, such as the posterior parietal cortex. Damage to the RSC severely impairs allocentric representations of the environment, including the ability to derive navigational information from landmarks. The specific deficits seen in tests of human and rodent navigation suggest that the RSC supports allocentric representation by processing the stable features of the environment and the spatial relationships among them. In addition to spatial cognition, the RSC plays a key role in contextual and episodic memory. The RSC also contributes importantly to the acquisition and consolidation of long-term spatial and contextual memory through its interactions with the hippocampus. Within this framework, the RSC plays a dual role as part of the feedforward network providing sensory and mnemonic input to the hippocampus and as a target of the hippocampal-dependent systems consolidation of long-term memory

Cortico-spinal modularity in the parieto-frontal system: a new perspective on action control

: Classical neurophysiology suggests that the motor cortex (MI) has a unique role in action control. In contrast, this review presents evidence for multiple parieto-frontal spinal command modules that can bypass MI. Five observations support this modular perspective: (i) the statistics of cortical connectivity demonstrate functionally-related clusters of cortical areas, defining functional modules in the premotor, cingulate, and parietal cortices; (ii) different corticospinal pathways originate from the above areas, each with a distinct range of conduction velocities; (iii) the activation time of each module varies depending on task, and different modules can be activated simultaneously; (iv) a modular architecture with direct motor output is faster and less metabolically expensive than an architecture that relies on MI, given the slow connections between MI and other cortical areas; (v) lesions of the areas composing parieto-frontal modules have different effects from lesions of MI. Here we provide examples of six cortico-spinal modules and functions they subserve: module 1) arm reaching, tool use and object construction; module 2) spatial navigation and locomotion; module 3) grasping and observation of hand and mouth actions; module 4) action initiation, motor sequences, time encoding; module 5) conditional motor association and learning, action plan switching and action inhibition; module 6) planning defensive actions. These modules can serve as a library of tools to be recombined when faced with novel tasks, and MI might serve as a recombinatory hub. In conclusion, the availability of locally-stored information and multiple outflow paths supports the physiological plausibility of the proposed modular perspective

Neural codes for one’s own position and direction in a real-world “vista” environment

Humans, like animals, rely on an accurate knowledge of one’s spatial position and facing direction to keep orientated in the surrounding space. Although previous neuroimaging studies demonstrated that scene-selective regions (the parahippocampal place area or PPA, the occipital place area or OPA and the retrosplenial complex or RSC), and the hippocampus (HC) are implicated in coding position and facing direction within small-(room-sized) and large-scale navigational environments, little is known about how these regions represent these spatial quantities in a large open-field environment. Here, we used functional magnetic resonance imaging (fMRI) in humans to explore the neural codes of these navigationally-relevant information while participants viewed images which varied for position and facing direction within a familiar, real-world circular square. We observed neural adaptation for repeated directions in the HC, even if no navigational task was required. Further, we found that the amount of knowledge of the environment interacts with the PPA selectivity in encoding positions: individuals who needed more time to memorize positions in the square during a preliminary training task showed less neural attenuation in this scene-selective region. We also observed adaptation effects, which reflect the real distances between consecutive positions, in scene-selective regions but not in the HC. When examining the multi-voxel patterns of activity we observed that scene-responsive regions and the HC encoded both spatial information and that the RSC classification accuracy for positions was higher in individuals scoring higher to a self-reported questionnaire of spatial abilities. Our findings provide new insight into how the human brain represents a real, large-scale “vista” space, demonstrating the presence of neural codes for position and direction in both scene-selective and hippocampal regions, and revealing the existence, in the former regions, of a map-like spatial representation reflecting real-world distance between consecutive positions

Cognition in vestibular disorders: state of the field, challenges, and priorities for the future

Vestibular disorders are prevalent and debilitating conditions of the inner ear and brain which affect balance, coordination, and the integration of multisensory inputs. A growing body of research has linked vestibular disorders to cognitive problems, most notably attention, visuospatial perception, spatial memory, and executive function. However, the mechanistic bases of these cognitive sequelae remain poorly defined, and there is a gap between our theoretical understanding of vestibular cognitive dysfunction, and how best to identify and manage this within clinical practice. This article takes stock of these shortcomings and provides recommendations and priorities for healthcare professionals who assess and treat vestibular disorders, and for researchers developing cognitive models and rehabilitation interventions. We highlight the importance of multidisciplinary collaboration for developing and evaluating clinically relevant theoretical models of vestibular cognition, to advance research and treatment

The Aha! Experience of Spatial Reorientation

The experience of spatial re-orientation is investigated as an instance of the wellknown phenomenon of the Aha! moment. The research question is: What are the visuospatial conditions that are most likely to trigger the spatial Aha! experience? The literature suggests that spatial re-orientation relies mainly on the geometry of the environment and a visibility graph analysis is used to quantify the visuospatial information. Theories from environmental psychology point towards two hypotheses. The Aha! experience may be triggered by a change in the amount of visual information, described by the isovist properties of area and revelation, or by a change in the complexity of the visual information associated with the isovist properties of clustering coefficient and visual control. Data from participants’ exploratory behaviour and EEG recordings are collected during wayfinding in virtual reality urban environments. Two types of events are of interest here: (a) sudden changes of the visuospatial information preceding subjects' response to investigate changes in EEG power; and (b) participants brain dynamics (Aha! effect) just before the response to examine differences in isovist values at this location. Research on insights, time-frequency analysis of the P3 component and findings from navigation and orientation studies suggest that the spatial Aha! experience may be reflected by: a parietal alpha power decrease associated with the switch of the representation and a frontocentral theta increase indexing spatial processing during decision-making. Single-trial time-frequency analysis is used to classify trials into two conditions based on the alpha/theta power differences between a 3s time-period before participants’ response and a time-period of equal duration before that. Behavioural results show that participants are more likely to respond at locations with low values of clustering coefficient and high values of visual control. The EEG analysis suggests that the alpha decrease/theta increase condition occurs at locations with significantly lower values of clustering coefficient and higher values of visual control. Small and large decreases in clustering coefficient, just before the response, are associated with significant differences in delta/theta power. The values of area and revelation do not show significant differences. Both behavioural and EEG results suggest that the Aha! experience of re-orientation is more likely to be triggered by a change in the complexity of the visual-spatial environment rather than a change in the amount, as measured by the relevant isovist properties

The hippocampus and spatial constraints on mental imagery

We review a model of imagery and memory retrieval based on allocentric spatial representation by place cells and boundary vector cells (BVCs) in the medial temporal lobe, and their translation into egocentric images in retrosplenial and parietal areas. In this model, the activity of place cells constrain the contents of imagery and retrieval to be coherent and consistent with the subject occupying a single location, while the activity of head-direction cells along Papez's circuit determine the viewpoint direction for which the egocentric image is generated. An extension of this model is discussed in which a role for grid cells in dynamic updating of representations (mental navigation) is included. We also discuss the extension of this model to implement a version of the dual representation theory of post-traumatic stress disorder (PTSD) in which PTSD arises from an imbalance between weak allocentric hippocampal-mediated contextual representations and strong affective/sensory representations. The implications of these models for behavioral, neuropsychological, and neuroimaging data in humans are explored

Long-term memory encoding of facial information in humans: an EEG and tACS study

In recent years, the investigation of memory formation and retrieval has attracted increasing interest. As oscillatory activity plays a crucial role in neuroplastic processes, episodic memory is to a considerable extent attributable to synaptic changes, synchronization, and neurophysiological alterations through oscillating electric fields. Perception processes are part of episodic memory encoding. Human face perception and encoding arouse particular interest due to their fundamental relevance in social behavior. This study aimed to determine the causal role of brain dynamics in the encoding of facial episodic memory in humans. As recent studies revealed an enhancement in cognitive processes by the entrainment of internal brain oscillations, tACS stepped up as a new method of non-invasive brain stimulation to induce neuroplasticity (Antal et al. 2008; Antal and Herrmann 2016). It is a promising tool to test the role of brain oscillations on episodic memory encoding in humans and the potential for memory improvement. For the entire study, we developed a memory task that includes encoding, a Short-Term Memory Retrieval Part, maintenance, and a Long-Term Memory Retrieval Part. In the longterm face recognition, we assessed both the performance and the choice confidence on the 3-point scale. Two consecutive experiments were performed. For the first experiment (20 participants), we used 128-channel EEG to identify the region of the brain that is exclusively responsible for the long-term face encoding and the frequency of the brain rhythm that is associated with the successful subsequent recognition. Then, we conducted the tACS experiment (25 participants) based on the frequency and spatial data from the EEG experiment. We implemented a double-blinded, randomized, counterbalanced, crossover, and placebo-controlled study design. 20 minutes of 4 Hz-tACS at 3 mA peak-to-peak were applied during the encoding task to the identified right or to the left TPO area for active control. One more session included sham stimulation to one or the other area. The EEG study revealed a significant synchronization of brain oscillations during successful long-term facial memory encoding in the right TPO area at the low theta range (4 Hz). In complete agreement, the placebo-controlled tACS study showed a significant enhancement of long-term memory recognition performance after the low theta-stimulation of the right but not the left TPO area. The results indicate that low theta oscillations in the right TPO area are vital for successful episodic long-term memory encoding of facial stimuli. Secondly, we confirm that active low theta-tACS applied on this area during encoding improves the subsequent memory recognition performance. This supports the concept of lateralization for face processing in the right posterior brain region; moreover it puts forward this area as a crucial neocortical node in communication with the hippocampus for the long-term memory encoding (Pitcher et al. 2011; Geib et al. 2017). The results are in agreement with other studies that revealed a positive correlation between theta power and memory performance (Pahor and Jaušovec 2014; Clouter et al. 2017). However, the present work reveals a causal link between the empowered low theta in the right TPO area and enhanced subsequent long-term memory recognition. In summary, tACS is a highly suitable non-invasive tool to entrain local neocortical low theta activity and enhance long-term memory encoding, which is important in the clinical context for revealing novel therapeutic strategies in prosopagnosia and prosopamnesia.2021-09-1