Neural Dynamics of Multiple Object Processing in Mild Cognitive Impairment and Alzheimer’s Disease: Future Early Diagnostic Biomarkers?

Abstract

The aim of this study was to investigate the behavioral and electrophysiological dynamics of multiple object processing (MOP) in mild cognitive impairment (MCI) and Alzheimer's disease (AD), and to test whether its neural signatures may represent reliable diagnostic biomarkers. Behavioral performance and event-related potentials [N2pc and contralateral delay activity (CDA)] were measured in AD, MCI, and healthy controls during a MOP task, which consisted in enumerating a variable number of targets presented among distractors. AD patients showed an overall decline in accuracy for both small and large target quantities, whereas in MCI patients, only enumeration of large quantities was impaired. N2pc, a neural marker of attentive individuation, was spared in both AD and MCI patients. In contrast, CDA, which indexes visual short term memory abilities, was altered in both groups of patients, with a non-linear pattern of amplitude modulation along the continuum of the disease: a reduction in AD and an increase in MCI. These results indicate that AD pathology shows a progressive decline in MOP, which is associated to the decay of visual short-term memory mechanisms. Crucially, CDA may be considered as a useful neural signature both to distinguish between healthy and pathological aging and to characterize the different stages along the AD continuum, possibly becoming a reliable candidate for an early diagnostic biomarker of AD pathology.

Connectivity alterations underlying the breakdown of pseudoneglect: New insights from healthy and pathological aging

“…This influential model predicts that the over-recruitment of brain areas serves as compensatory activity against deterioration processes ( Reuter-Lorenz et al, 2000 ; Cabeza et al, 2002 ). Compensatory mechanisms, however, may also be lateralized in the brain as is the case of the contralateral delay activity (CDA), an EEG neural marker of the multiple object enumeration process that was found to be able to capture hemispheric lateralization in older adults ( Bagattini et al, 2017 ; Sander et al, 2019 ).…”

“…Three age-matched groups of participants were included in this study: 14 patients with a clinical diagnosis of mild AD (seven females, mean age = 74.9, SD = 6.0, range = 63–83), 15 amnesic patients with MCI (six females, mean age = 74.5, SD = 5.9, range = 60–81), and 14 healthy elderly controls (HC; 9 females, mean age = 70.9, SD = 3.8, range = 67–82). Data from these participants were included in Bagattini et al (2017) and partly in Brignani et al (2018) . Clinical diagnosis of AD and amnesic MCI was done by expert neurologists or geriatricians addressing medical history, clinical examination, neuropsychological testing, and imaging results such as computed tomography, MRI, or PET.…”

“…Target numerosity was classified as a two-level factor (low and high) as in a previous study the factor visual hemifield showed a significant interaction with numerosity, suggesting that the pseudoneglect effect was modulated by the number of targets presented, with a greater leftward bias for high numerosity ( Brignani et al, 2018 ). Furthermore, the mean subitizing span (i.e., the number of targets that can be processed simultaneously before counting processes come into play) for patients with AD, patients with aMCI, and HC was 3.17 targets ( Bagattini et al, 2017 ). A semi-automatic procedure based on the threshold criterion (± 100 μV) was then applied to remove muscular and ocular artifacts.…”

Treatment effects on event-related EEG potentials and oscillations in Alzheimer's disease

“…In a recent review paper, 22% of reviewed studies between MCI and CU groups reported a significant difference in N200 amplitude, while the rate was 18% between ADD and CU groups (Paitel et al, 2021). More specifically, some studies reported smaller N200 amplitude in both MCI and ADD groups over the CU groups (Fernandez et al, 2013;Wang et al, 2013;Bagattini et al, 2017), while some others stated no difference in N200 between MCI and CU groups (Cespón et al, 2015a;Mudar et al, 2016) or between CU and ADD groups (Bagattini et al, 2017). The abovemixed results might be due to the different variants of the oddball tasks used as the kind of stimuli, the inter-stimulus intervals, the task duration, the level of required attention to the stimuli and experimental conditions, and the kind of subject's responses required during ERP recordings (Morrison et al, 2019).…”

If it looks, sounds, or feels like subitizing, is it subitizing? A modulated definition of subitizing

“…These theories were examined and discussed not just using behavioral methods but also with neuroimaging methods (e.g., in Cutini, Scatturin, Basso Moro, & Zorzi, 2014;Leibovich, Henik, & Salti, 2015;Piazza et al, 2002), with abnormal populations (Ashkenazi et al, 2013;Bagattini et al, 2017;Dehaene & Cohen, 1994;Gagnon, Mottron, Bherer, & Joanette, 2004;Mazza, 2017), and in other modalities.…”