A unified brain system of orientation and its disruption in Alzheimer’s disease

Abstract

ObjectiveTo investigate whether a unified brain system manages one’s orientation to different places, events and people in one’s environment, and test the hypothesis that failure of this system (disorientation) is an early sign of Alzheimer’s disease (AD).MethodsA total of 46 participants (patients along the AD continuum and cognitively normal control subjects) were tested in a personalized, ecologically valid task of orientation relating to the participant’s own world in space, time and person under high–density electroencephalography. As a first step, we used evoked potential mapping to search for brain topography correlated with participants’ performance in orientating themselves to different places (space), events (time) and people (person) (Experiment 1). We then compared behavioral and electrophysiological changes in patients along the AD continuum (Experiment 2).ResultsWe identified a specific brain topography (“orientation map”) that was active for orientation in space, time and person in correlation to participants’ performance. Both performance and the map’s strength gradually decreased from health to mild cognitive impairment (MCI) and from MCI to AD. Another map, immediately preceding the orientation map, showed the longest activity in patients with MCI, significantly more than both patients with AD and cognitively normal controls.InterpretationOur findings demonstrate that the same brain topography accounts for orientation in the different domains of space, time and person and provide a nexus between deterioration in patients’ orientation with the aggravation of Alzheimer’s disease.

Short-term memory, attention, and temporal orientation as predictors of the cognitive impairment in older adults: A cross-sectional observational study

“…TO is a component used to diagnose cognitive impairment. It is among the first neuropsychological constructs to be impaired in AD [ 65 ]. TO presents a greater difference between subjects with MCI or dementia and those without impairment [ 66 ].…”

Lost in space(s): multimodal neuroimaging of disorientation along the Alzheimer’s disease continuum

“…See supplementary materials for more details. The task was modeled on our previous studies of orientation (Dafni-Merom et al, 2019;Hayman & Arzy, 2021;Peer et al, 2015; Efficacy scores (ES) (Townsend & Ashby, 1983) were computed for each participant and domain separately by calculating the ratio between the success rate (SR) and mean response time (RT). A global ES was calculated for each participant by averaging the ESs across the three domains.…”

“…However, orientation is not restricted to the spatial domain. It involves other domains such as the temporal and social ones (Du, Basyouni, & Parkinson, 2021; Parkinson, Liu, & Wheatley, 2014; Peer et al, 2015), that have been shown to be progressively impaired along the AD-continuum (Dafni-Merom, Peters-Founshtein, Kahana-Merhavi, & Arzy, 2019; Peters-Founshtein et al, 2018). Moreover, tests of orientation have been found to better discriminate between cognitively normal (CN) and mild cognitive impairment (MCI) participants (95% accuracy) when compared to standard neuropsychological evaluations (Addenbrooke’s Cognitive Examination (ACE) – 71%, Mini Mental State Examination (MMSE) – 70%) (Peters-Founshtein et al, 2018).…”

The role of temporal distance of the events on the spatiotemporal dynamics of mental time travel to one’s personal past and future

“…Among neuroimaging techniques, electroencephalography (EEG) has a far better temporal resolution than fMRI, allowing for more precise observations of the temporal dynamics of the cognitive processes studied. In a recent EEG study exploring disorientation in Alzheimer's disease, Dafni-Merom et al 40 showed that one’s orientation to different places, events and people elicited a comparable brain topography as early as around 200 ms (as compared with a control condition), effects that could not have been observed on a fMRI study. Compared to the fMRI literature, however, studies using EEG to analyze the brain activation patterns of mental time travel to the past and the future are scarce 41 – 44 .…”