Mechanisms underlying memory enhancement in humans

  1. Yebra Granados, María del Mar
Dirigée par:
  1. Bryan Strange Directeur/trice

Université de défendre: Universidad Politécnica de Madrid

Fecha de defensa: 09 juin 2017

Jury:
  1. Nikolai Axmacher President
  2. Stephan Moratti Secrétaire
  3. Guglielmo Foffani Rapporteur
  4. Antonio Oliviero Rapporteur
  5. Javier Jesús González Rosa Rapporteur

Type: Thèses

Résumé

Memory has been a focus of intensive research since the 1800s. Currently, we know of several factors that modulate episodic memory, such as emotions, reward, unexpected events and semantic relations. However the mechanisms underlying this modulation remain unknown in humans. This thesis explores the neural bases of two factors which influence memory –actions and unexpectedness. Movement is not typically considered a factor that modulates memory but in the 1960s a possible relationship between movement and memory was suggested by evidence that lesions of the hippocampus–a region with a key role in episodic memory- provoked hyperactivity in rodents. Later studies in humans have confirmed a relationship between voluntary movement and hippocampal activity, but little is currently known about the relationship between motor and memory systems. In this thesis the hypothesis that voluntary movements, completely unrelated with the memory content, influence episodic memory is tested in humans. Across a series of behavioral experiments, a voluntary movement-evoked episodic memory enhancement was found. Furthermore, fMRI and pupilometry analysis revealed that this memory enhancement is mediated by the noradrenergic system. In addition, functional connectivity was observed between the Locus Coeruleus –the main source of noradrenaline in the brain-, and the parahippocampal gyrus –a region known to represent an important role in episodic memory encoding. This implies that a voluntary movement triggers the release of noradrenaline in the brain that targets memory areas to promote episodic memory encoding. Another factor known to modulate episodic memory is novelty, which can be defined as any event that represents a mismatch between expectation and experience. Hippocampal damage impairs the acquisition of novel episodic memories, which may suggest a role in processing novel stimuli. Hippocampal responses to novelty stimuli has been studied in animals and humans with different functional neuroimaging and electrophysiological techniques, however differences in the novelty processing along the long axis of the hippocampus remain unknown. Anatomical, functional, connectivity and genetic differences have been shown along the long axis of the hippocampus. A functional role of theta oscillatory frequency has been ascribed along the longitudinal axis in rodents decreasing from dorsal to ventral portions in rodents concomitant with an increase in place field size. A systematic evaluation of gamma and theta frequencies along the longitudinal axis has not been done in humans. In this thesis electrophysiological correlates with novelty have been studied along the longitudinal axis of the human hippocampus in pharmaco-resistant epileptic patients using intracranial electroencephalography (iEEG) recordings. A polarity inversion of the event related potential between the head and the body observed, lead us to suggest a possible electrical novelty-evoked source within the anterior portion of the hippocampus. Different portions of the hippocampus (head, body and tail) show a within-region power increase in theta and gamma frequency bands, reflecting increased local activity in each longitudinal portion during novelty processing. Analysis of phase locking value and imaginary coherence revealed between-region theta coherence increase. However, phase locking values were not affected by unexpectancy indicating that different portions of the hippocampus were similarly synchronized. This consistent phase relationship in theta between portions of the hippocampus led us to test for the presence of traveling waves along the hippocampal long-axis (as has been recently shown in rodents and in limited number of human patients). We confirmed theta (and alpha) traveling wave pattern along the long axis of the hippocampus from posterior to anterior segments. This implies that the hippocampus experiences different phases of theta and alpha frequencies at the same time, potentially representing a mechanism for coding information. No differences on the lower frequencies modulating the gamma envelope during novelty processing across the long-axis were observed. Despite known differences along the long axis of the hippocampus and previous studies showing a functional segregation in novelty processing between anterior and posterior hippocampal portions, results in this thesis suggest common oscillatory response properties across the long-axis. Different approaches have been used in this thesis to study different factors that modulate episodic memory in humans: actions and novelty. The first demonstration of voluntary movement-evoked modulation of memory for stimuli unrelated to the action is described, as well as a mechanistic account for this effect mediated by noradrenergic system. Next, a comprehensive evaluation of the electrophysiological response to novelty in human hippocampus is presented, with focus on commonalities and differences in response properties along the different portions of the hippocampal long axis.