Regional Precuneus Cortical Hyperexcitability in Alzheimer's Disease Patients

Abstract

Objective Neuronal excitation/inhibition (E/I) imbalance is a potential cause of neuronal network malfunctioning in Alzheimer's disease (AD), contributing to cognitive dysfunction. Here, we used a novel approach combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to probe cortical excitability in different brain areas known to be directly involved in AD pathology. Methods We performed TMS‐EEG recordings targeting the left dorsolateral prefrontal cortex (l‐DLPFC), the left posterior parietal cortex (l‐PPC), and the precuneus (PC) in a large sample of patients with mild‐to‐moderate AD (n = 65) that were compared with a group of age‐matched healthy controls (n = 21). Results We found that patients with AD are characterized by a regional cortical hyperexcitability in the PC and, to some extent, in the frontal lobe, as measured by TMS‐evoked potentials. Notably, cortical excitability assessed over the l‐PPC was comparable between the 2 groups. Furthermore, we found that the individual level of PC excitability was associated with the level of cognitive impairment, as measured with Mini‐Mental State Examination, and with corticospinal fluid levels of Aβ42. Interpretation Our data provide novel evidence that precuneus cortical hyperexcitability is a key feature of synaptic dysfunction in patients with AD. The current results point to the combined approach of TMS and EEG as a novel promising technique to measure hyperexcitability in patients with AD. This index could represent a useful biomarker to stage disease severity and evaluate response to novel therapies. ANN NEUROL 2023;93:371–383

Frontotemporal Dementia, Where Do We Stand? A Narrative Review

“…In recent years, novel neurophysiological techniques, such as transcranial magnetic stimulation (TMS), have been investigated in neurodegenerative diseases to better characterise some aspects of cortical circuitry, plasticity, reactivity, and connectivity [228,229]. Undoubtedly, the most investigated pathology has been AD, in which several correlations with neuropsychological and neuropathological biomarkers have been made, showing that AD is characterised by an impairment of cortical plasticity, hyperexcitability, and altered connectivity [230], mirroring the neuropathological studies in animal models [231].…”

Unlocking the Potential of Repetitive Transcranial Magnetic Stimulation in Alzheimer’s Disease: A Meta-Analysis of Randomized Clinical Trials to Optimize Intervention Strategies

“…TMS stimulation led to pronounced excitability in the DLPFC [73], a crucial element in cortical plasticity and cognitive function [74]. The findings suggest that rTMS holds promise as an efficacious intervention for AD by augmenting cortical excitability [19,[75][76][77] and enduring neuroplasticity alterations [51,78,79]. Furthermore, some studies indicated that post-TMS treatment, neural activity in the anterior cingulate cortex was enhanced, brain oscillations in the beta band intensified, and functional connections between the anterior cingulate cortex and medial frontal lobe region of the default mode network (DMN) were transformed [80].…”

Alterations in gamma frequency oscillations correlate with cortical tau deposition in Alzheimer’s disease

“…Tau protein accumulation is known to promote network hyperexcitability and in an AD murine model its reduction resulted in a decreased hyperexcitability, independently from the presence of Aβ42 (Tok, Ahnaou, and Drinkenburg 2022). Moreover, a recent study in AD patients found a positive linear correlation between the amplitude of the TMS-evoked potential (TEP) at the level of the posterior parietal cortex and the levels of tau and p-tau in CSF (Casula et al 2022). Hence, we hypothesize that the presence of tau protein and neurodegeneration could locally disrupt of the physiological rhythms, forcing the remaining neurons to increase their activity, to maintain the excitatory/inhibitory balance.…”