Autobiographical memory, time and space into an integrated neuropsychological perspective: insights from pathological and healthy functioning

Autobiographical memory (AM) represents a complex and multicomponential cognitive function that comprises memory systems that allow an individual to encode, consolidate and retrieve personal events and facts (Fossati, 2013). Two major components can be distinguished in AM: episodic and semantic. Episodic autobiographical memory (EAM) concerns the ability to recall personal events occurred in a specific time and place, that can be recollected through a rich sensory-perceptual and emotional context that enables to re-experience that past moment; semantic autobiographical memory (SAM) refers to facts and knowledge about the self (Levine, 2004) that are abstract and generalized forms of personal semantics (PS) which lack the context of acquisition (Renoult et al., 2012). EAM is deeply connected to autonoetic consciousness, namely the subjective experience of mentally travel back in time and relieve an event (Wheeler et al., 1997), through the process of re-experiencing, as well as features of vivid visual imagery from a first-person perspective (Zaman et al., 2024). Autobiographical memory has been conceived to be organized into partonomic hierarchical levels of specificity ranging from 1) lifetime periods, that refer to general knowledge of significant others, common locations, activities, plans, and goals, characteristic of a period; 2) general events, that concern events linked together by a theme; and 3) event-specific knowledge, such as events occurred at a specific time and place (Conway & Pleydell-Pearce, 2000). In this framework, AM is strictly connected to the self with an adaptive process to maintain coherence through time (Conway, 2005). Episodic autobiographical memory relies on a wide network of brain areas, including the posterior cingulate cortex, the parahippocampal gyrus, the ventromedial prefrontal cortex, the angular gyrus, and the anterior middle temporal gyrus, the temporal pole and the superior frontal gyrus (Boccia, Teghil, et al., 2019; Svoboda et al., 2006). The contribution of the medial temporal lobe, particularly the hippocampus, to episodic memory is well established (Eichenbaum et al., 2012): the hippocampal formation, together with connections to the entorhinal cortex, represents a central node in defining the spatial and temporal context of episodic memory (Ekstrom & Ranganath, 2018; Sugar & Moser, 2019). It has been proposed that the discharge properties of the “place cells” and “grid cells” within this brain network may form the basis of the organization of cognitive spaces (Bellmund et al., 2018; Constantinescu et al., 2016) and that the phylogenetic origins of declarative memory lie in these mechanisms (Buzsáki & Moser, 2013). At the same time, it has been proposed that “time cells” in the hippocampus, which discharge at specific moments in time, may encode the temporal organization of events (Sugar & Moser, 2019). Neuroimaging studies show that the ability to relive an episode in a rich and detailed manner is mediated by the hippocampus due to its ability to create associations from the spatial and temporal context (Diana et al., 2007). Accordingly, brain regions that are fundamental in environmental navigation partially overlap with those of autobiographical memory, including the bilateral posterior cingulate cortex, parahippocampal cortex and hippocampus, and the right angular gyrus (Teghil, Bonavita, et al., 2021). Also, “time cells” within the hippocampus firing at specific timepoints (MacDonald et al., 2011), have been suggested to represent a neural substrate central in encoding temporal information allowing to organize events (Sugar & Moser, 2019). In this framework, the core hypothesis of this dissertation is that past events are organized into a cognitive map indexed through a temporal code. To better investigate this hypothesis behavioural and neuroimaging data will be acquired in different pathological conditions, such that an impairment in episodic autobiographical memory involves an alteration of spatial and temporal processing. Traumatic Brain Injury (TBI) will be used as a first lesion model to test the current hypothesis in Study 2. A consequence of external forces acting in TBI is diffuse axonal injury together with other pathophysiological processes that hesitate in EAM impairments (Bischof & Cross, 2023; Maas et al., 2022). Given the distributed network sustaining EAM (Svoboda et al., 2006), TBI represents a model to investigate mechanisms underlying this function. Also, Focal Brain Damage (FBD) due to stroke represents another model to deeply investigate the relation between spatiotemporal processing and EAM. Thus, in Study 3 behavioural and voxel-based lesion symptom mapping as well as atlas-based hodological analyses will be combined to deepen this relation. Pathological ageing has been found to be connected to a decline in both spatial (Verghese et al., 2017) and temporal processing (Mioni et al., 2021). In particular, amnestic Mild Cognitive Impairment (aMCI) will be used in Study 5 as a model to test the hypothesis that a decline in EAM is associated with spatiotemporal processing. Also, voxel-based morphometry will be used to investigate the relation with a reduction in gray matter volume in key nodes of EAM (hippocampus, parahippocampal gyrus, and entorhinal cortex). A stage that has been proposed as a potential early marker of cognitive changes in preclinical Alzheimer’s Disease (Rabin et al., 2017) will be used as a model to investigate possible cognitive markers in this condition, that is characterized by a subjective worsen of cognitive functioning without a corresponding objective impairment (Jessen, Amariglio, et al., 2014). Thus, in Study 4 the relation between spatiotemporal processing and EAM will be investigated in a group of individuals with Subjective Cognitive Decline (SCD). In Study 6 will be deepened our knowledge about Severely Deficient Autobiographical Memory (Conti et al., 2023; Palombo, Alain, Söderlund, et al., 2015), combining behavioural and neuroimaging data in a group of healthy individuals complaining lifelong impairments in re-experiencing past events; both group and single-case methodologies will be adopted to investigate possible common patterns, as well as focusing on features pertaining to each individual. Finally, Study 1 will be focused on the validation of the Autobiographical Fluency Task (Conti et al., 2024), a feasible instrument to assess autobiographical memory, especially for testing episodic autobiographical memory and experience-near personal semantics in clinical settings.