Multimodal characterization and modulation of large-scale memory networks: Implications for cognitive aging

• Autores: Didac Vidal Piñeiro
• Directores de la Tesis: David Bartrés Faz (dir. tes.)
• Lectura: En la Universitat de Barcelona ( España ) en 2014
• Idioma: inglés
• Tribunal Calificador de la Tesis: Pere Vendrell Gómez (presid.), Diego Redolar Ripoll (secret.), Marie-laure Paillere Martinot (voc.)
• Materias:
  • Psicología
    • Psicología experimental
      • Actividad cerebral
    • Psicología de la vejez
• Enlaces
  • Tesis en acceso abierto en:  TDX  Dipòsit Digital de la UB 
• Resumen

  • As neurocognitive decline is probably the greatest threat to healthy aging in our society it is necessary to know the factors that are associated with neurocognitive frailty or protection such as the expression of brain networks that support cognition. Aging is characterized by several cognitive changes including significant decreases of long-term episodic memory. Different structures especially the medial temporal lobe (MTL), the prefrontal cortex (PFC) and the Default-Mode Network (DMN) regions are essential for this cognitive function. Neuroimaging techniques characterized aging, among others, as alterations in the expression of large-scale functional networks; usually assessed with functional magnetic resonance imaging (fMRI). On the other hand, plasticity can be conceptualized as an intrinsic property of the human brain that allows to overcome the limitations of the genome and to adapt to environmental pressures, physiological changes and experiences thus being essential for learning and memory, while reduced in aging and several neurodegenerative disorders. The study of the mechanisms of plasticity in humans has greatly benefited from the introduction of noninvasive brain stimulation techniques as they allow the characterization of local plasticity mechanisms and a causal approximation to the study of brain networks. One of this is transcranial magnetic stimulation (TMS) which is based on the principle of electromagnetic induction acting through brief application of magnetic fields and causing depolarization of the underlying neurons. Combined with other techniques such as fMRI or MR spectroscopy (MRS) is able to measure induced brain effects outside the motor cortex. Repetitive TMS transiently induce changes in the activity of underlying (and distal interconnected) regions which lasts several minutes and are understood as induction of cortical plasticity mechanisms. Induced-TMS changes in cortical excitability can provoke behavioral and cognitive changes and allow to study the involvement of certain regions in specific process and to assess the state of local cortical plasticity mechanisms thus helping to understand mechanisms underlying cognitive changes. The main objective of this thesis is to characterize and modulate large-scale networks involved in episodic memory, with a special focus on the implication and application in cognitive aging through the use of multimodal neuroimaging and induction controlled experimentally, mechanisms of cortical plasticity. A second object is to reveal the relationship between plasticity mechanisms, studied through the TBS, and the intrinsic brain connectivity assessed by fMRI. Three studies have been carried: The first study has been focused on the modulation of memory function and networks through the application of TMS. The second was centered on the relationship between anteroposterior DMN connectivity and structural and perfusion measures in healthy elders. The third study was focused on the implementation of a protocol able to produce regional neurotransmitters concentration modulations in key DMN node through TMS (evaluated with MRS). The main conclusions are: 1) large-scale brain networks, specifically frontal and DMN networks are fundamental to understand decline and preservation of episodic memory in aging. 2) Anteroposterior DMN connectivity is decreased in aging and predicts memory function. 3) In aging, anteroposterior DMN connectivity relates to the grey and white matter integrity in areas of high age-related susceptibility. 4) The left inferior frontal cortex exerts top-down influences over primary visual areas specifically during semantic encodings. 5) TMS over memory networks is able to induce physiological changes that persist the period of stimulation in local and distal regions reflected by BOLD and neurotransmitter concentration changes. 6) TMS effect shows a state­dependency effect regarding brain connectivity. 7) Neurotransmitter modulation after TMS is a useful tool to assess the state of local plasticity mechanisms in critical areas of both the healthy and pathological aging brain.